Biomedical subjects

U Knigge

Publications and source records attributed to U Knigge.

At least 37 records · Page 2Linked to original sources

PubMed1997

Influence of Naloxone on the cellular immune response to head-up tilt in humans.

To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.

Adult↗

PubMed1997

Histamine and prostaglandin interaction in the central regulation of ACTH secretion.

Since prostaglandins (PGs) and histamine (HA) seem to be involved in the activation of the hypothalamic-pituitary-adrenal axis following immunochallenges with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether the histaminergic and eicosanoid systems in the male rat brain interact in their regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg i.p.) attenuated the ACTH response to LPS (10 micrograms/kg i.p.) and HA (30 micrograms i.c.v.). Infusion of PGE1, PGE2 or PGF2 alpha (1 and/or 5 micrograms infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response to PGE1 was inhibited by the HA synthesis inhibitor alpha-fluoromethyl-histidine and the H1 receptor antagonist mepyramine (MEP) but not the H2 receptor antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to PGE2. MEP and CIM attenuated the ACTH response induced by PGF2 alpha. The findings indicate that HA and some PGs in the brain interact in their stimulatory regulation of ACTH secretion. Such an interaction may also be involved in their mediation of the ACTH response to immunochallenges.

Adrenocorticotropic Hormone↗

PubMed1996

Gentamicin concentrations in human subcutaneous tissue.

Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug concentrations in serum and subcutaneous interstitial fluid were obtained simultaneously for 6 h. The tissue gentamicin concentration peaked after 10 to 30 min. The peak concentration in the tissue was 6.7 +/- 2.0 mg.liter-1 (standard deviation), equivalent to 39.1% of the peak concentration in serum. The area under the concentration-versus-time curve for the first 6 h in the tissue was 1,281 +/- 390.0) mg.min liter-1, equivalent to 59.7% of the area under the concentration-versus-time curve in serum. It is concluded that the microdialysis technique can be used to make dynamic and quantitative measurements of the gentamicin concentration in human subcutaneous tissue. In this adipose tissue, the peak concentrations of gentamicin were approximately seven times the MIC for Pseudomonas aeruginosa and 33 times the MIC for Staphylococcus aureus after the administration of an intravenous bolus of 240 mg, indicating the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria.

Adipose Tissue↗

PubMed1996

Involvement of histamine in suckling-induced release of oxytocin, prolactin and adrenocorticotropin in lactating rats.

We have previously shown that histaminergic neurons participate in mediation of the prolactin (PRL), adrenocorticotropin (ACTH) and oxytocin responses to physiological stimuli such as stress and dehydration. Since suckling is a potent stimulus for the secretion of these three hormones, we investigated the mediating role of neuronal histamine in suckling-induced release of oxytocin, PRL and ACTH in conscious lactating rats. The animals were pretreated with the histamine synthesis inhibitor alpha-fluoromethylhistidine, the H1 receptor antagonist mepyramine, the H2 receptor antagonist cimetidine or the H3 receptor agonist R (alpha) methylhistamine, which by binding to H3 autoreceptors inhibits histamine release and synthesis. After the lactating rats were separated from their pups for 240 min, the pups were returned for a suckling period of 20 min. Thereafter the mothers were sacrificed by decapitation and trunk blood was collected for determination of hormones. Lactating rats not exposed to suckling served as controls. Suckling increased oxytocin 2-fold, PRL 50-fold and ACTH 5-fold. Blockade of histamine synthesis by alpha-fluoromethylhistidine or histamine release by R(alpha)methylhistamine reduced the suckling-induced secretion of the three hormones significantly. Blockade of postsynaptic H1 receptors by mepyramine inhibited the hormone responses to suckling, while the blockade of postsynaptic H2 receptors by cimetidine decreased the suckling-induced oxytocin and PRL release but did not affect the ACTH release. None of the compounds affected oxytocin, PRL or ACTH secretion in lactating mothers not exposed to suckling. In addition, suckling significantly increased the mRNA of the histamine synthesizing enzyme histidine decarboxylase in the ventrolateral tuberomammillary nucleus by 1.5-fold, indicating that the stimulus of suckling enhances the neuronal histamine synthesis. We conclude that suckling increases neuronal histamine synthesis and that histaminergic neurons by activation of postsynaptic H1 and H2 receptors are involved in the hypothalamic mediation of oxytocin, PRL and ACTH responses to suckling. These findings further substantiate a role of neuronal histamine in the neuroendocrine regulation of pituitary hormones in response to physiological stimuli.

Adrenocorticotropic Hormone↗

PubMed1996

Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion.

Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1 + 2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5- HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H3 receptors are inhibitory HA receptors. Systemic pretreatment with the H3 receptor agonist R(alpha)methylhistamine, or the H3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx. We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H1 and H2 receptors. Furthermore, the previously observed inhibitory effect of the H3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H3 receptors located on serotonergic neurons but rather on histaminergic neurons.

5-Hydroxytryptophan↗

PubMed1995

Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind, randomized pilot study.

PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on survival in patients with colorectal carcinoma, a randomized, controlled pilot study was performed in three university hospitals in Copenhagen, Denmark. METHODS: A total of 192 patients, who had undergone a resection or an exploratory operation for adenocarcinoma of the colon or rectum between May 1988 and May 1991, were enrolled in the study. After a median observation time of 40 months, outcome was noted for each patient concerning cancer-specific mortality rate. RESULTS: In patients operated with curative intent (n = 148), no difference was found in cancer-specific mortality between the two treatments. However, a tendency toward reduction in mortality rate was found in patients with curatively operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29 percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine-treated group. In patients with disseminated disease no total difference was found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to reduce mortality in patients with colorectal cancer, but there seems to be a tendency toward a survival benefit in patients undergoing surgery for Dukes Stage C carcinoma. Results seem to justify trials in this patient category to reveal a benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

Adenocarcinoma↗

PubMed1995

Cardiovascular and hormonal responses to anaphylactic shock in the pig.

Cardiovascular and hormonal responses to anaphylactic shock were evaluated in anaesthetized pigs sensitized by natural exposure to Ascaris suum as verified by antibodies. In six animals with such antibodies, Ascaris antigen injection produced a plasma histamine increase of 52 (42-196) fold (median and range; P < 0.05), while four pigs without such antibodies served as controls with only insignificant increases in histamine. In the anaphylactic group, two of the animals died during the investigation due to cardiovascular collapse. In the sensitized pigs resting heart rate (HR), 104 (86-118) beats min-1, increased to 204 (164-240) beats min-1 as mean arterial pressure (MAP) decreased from 94 (83-102) to 45 (31-90) mmHg (P < 0.05). In contrast, the non-sensitized pigs maintained the resting HR of 101 (79-113) beats min-1, as MAP decreased to 50 (41-97) mmHg (P < 0.05). In the sensitized group systemic vascular resistance (SVR) fell from 1114 (843-1811) to 990 (588-1173) dyne s-1 cm-5 and then increased to 3617 (2593-4166) dyne s-1 cm-5, while in the control group there was only a reduction to a minimum value of 730 (458-1307) dyne s-1 cm-5 (P < 0.05). Thoracic electrical impedance increased only in the sensitized group [from 28.3 (24.7-31.4) to 29.9 (24.0-31.4)], indicating central volume depletion. Plasma catecholamines increased markedly only in the sensitized pigs, and plasma pancreatic polypeptide, vasopressin, aldosterone and renin responses confirmed to those established during central hypovolaemia. During anaphylaxis, this study demonstrated cardiovascular responses similar to those established during a major blood loss. However, as indicated by plasma catecholamines, sympathetic activity was many times that previously demonstrated during haemorrhage, and sympathoactivation may explain the marked vasoconstriction noted in the sensitized pigs.

Anaphylaxis↗

PubMed1995

Role of glucagon in maintenance of euglycemia in fed and fasted rats.

The role of glucagon in the regulation of blood glucose in fed and fasted anesthetized rats was studied by injecting intravenously 4 ml/kg of a high-capacity (40 nmol/ml) high-affinity (0.6 x 10(11) mol/l) monoclonal glucagon antibody. Blood glucose was lowered by the antibody by 2 mmol/l in fed rats but remained unchanged in 10- and 48-h-fasted rats. Antibody injection significantly reduced plasma insulin in both fed and 10-h-fasted rats. In 10-h-fasted rats, propranolol injection decreased blood glucose by 0.6 mmol/l, and combined with antibody administration, a decrease by 1.1 mmol/l was observed. Blood glucose was never < 3.3 mmol/l. Thus glucagon is partly responsible for maintenance of euglycemia in fed rats, whereas during fasting it plays a limited role. However, immunoneutralization of glucagon reduces insulin secretion irrespective of blood glucose. Additional mechanisms seem to be responsible for the maintenance of blood glucose in the fasting state when glucagon and the sympathoadrenergic system are blocked.

Adrenergic Antagonists↗

PubMed1995

Stress-induced secretion of pro-opiomelanocortin-derived peptides in rats: relative importance of the anterior and intermediate pituitary lobes.

Stress stimulates secretion of the pro-opiomelanocortin (POMC)-derived peptides adrenocorticotropic hormone (ACTH), beta-endorphin (beta-END) and alpha-melanocyte-stimulating hormone (alpha-MSH) from the anterior lobe (AL) and intermediate lobe (IL) of the pituitary gland. The secretion of POMC-derived peptides from the AL and IL is differentially regulated and the relative contribution of the lobes may vary with the stimulus. We investigated (1) the relative importance of the AL and IL as source of POMC-derived peptides released in response to restraint and ether stress by selectively inhibiting the corticotropes of the AL by dexamethasone (DEX) or selectively inhibiting the melanotropes of the IL by bromocriptine (BR), and (2) whether beta-adrenergic blockade by propranolol could be used to discriminate between the stress-induced effect on POMC secretion from the AL and IL as has previously been suggested. Selective inhibition of AL secretion by DEX totally blocked the ACTH response to restraint and ether stress, but only partially inhibited the beta-END response. The alpha-MSH response to both stressors was not affected by DEX. Conversely, selective inhibition of IL secretion by BR totally blocked the alpha-MSH response to both stressors, partially inhibited the beta-END response but did not influence the ACTH response. In response to restraint stress, beta-END was secreted equally from the AL and IL, whereas the IL was the most important source of beta-END in response to ether stress. Blockade of beta-adrenergic receptors with propranolol inhibited the beta-END- and alpha-MSH responses to restraint stress whereas the ACTH response was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1995

Involvement of oxytocin in histamine- and stress-induced ACTH and prolactin secretion.

The neurohypophysial peptide oxytocin (OT) is released in response to different stressors and has been suggested as a 'stress hormone'. In addition, we have recently shown that centrally administered histamine (HA), which is a mediator of stress-induced release of ACTH and prolactin (PRL), stimulates OT secretion. The aim of the present investigation was to further characterize the HA-induced OT secretion with respect to the type of postsynaptic receptor involved and to investigate the possible role of OT in HA- and stress-induced ACTH and PRL secretion. We studied (1) the effect of HA, HA agonists and HA antagonists on OT secretion in normal male rats, (2) the secretion of OT in response to HA stimulation and to restraint stress, endotoxin stress [lipopolysaccharide (LPS) administration] and insulin/hypoglycemia stress and compared the OT response to that of arginine vasopressin (AVP), (3) the OT response to restraint stress or HA in normal and AVP-deficient Brattleboro rats (DI) suffering from diabetes insipidus and (4) the effect of inhibiting the oxytocinergic system by immunoneutralization or receptor blockade on HA- and stress-induced ACTH and PRL release in normal as well as in DI rats. HA, an H1 and an H2 receptor agonist, stimulated the OT secretion dose-dependently. The HA-induced release of OT was inhibited by pretreatment with an H1 or an H2 receptor antagonist. Restraint stress and HA but not LPS or insulin stress induced an increase in peripheral OT levels, whereas only LPS stress and HA caused an increase in circulating AVP levels. Neither an OT antiserum nor an OT antagonist inhibited the HA- or restraint-stress-induced ACTH or PRL release in normal rats. AVP-deficient DI rats showed, in comparison with their nondeficit counterparts, an increased basal level of OT and no increase in OT levels following restraint stress, whereas the OT response to HA was similar in the two rat types. In AVP-deficient rats immunoneutralization of OT had no inhibitory effect on the HA- and restraint-stress-induced ACTH and PRL response. The ACTH and PRL response to restraint stress and the ACTH response to HA was impaired in DI rats compared to their healthy controls. We conclude (1) that HA stimulates OT secretion via activation of postsynaptic H1 and H2 receptors, and (2) that, in contrast to AVP, OT does not seem to be involved in HA- and restraint-stress-induced ACTH and PRL secretion.

Adrenocorticotropic Hormone↗

PubMed1995

Effect of histamine on gene expression and release of proopiomelanocortin-derived peptides from the anterior and intermediate pituitary lobes in conscious male rats.

Via activation of H1 or H2 receptors histamine (HA) stimulates the secretion of proopiomelanocortin (POMC)-derived peptides from the anterior (AL) and intermediate (IL) pituitary lobes of male rats. During selective inhibition of the AL or IL by pretreatment with dexamethasone (Dx) or bromocriptine (Br), respectively, we studied the effect of equipotent doses of intracerebroventricularly infused HA, the H1-receptor agonist 2-thiazolylethylamine (2TEA) or the H2-receptor agonist 4-methy1HA (4MeHA) on the release of ACTH, beta-endorphin (beta-END) immunoreactivity (ir) and alpha-melanocyte-stimulating hormone (alpha-MSH) in conscious male rats. Dx blocked the ACTH responses whereas Br prevented the alpha-MSH responses. Dx and Br equally inhibited the response of beta-ENDir to HA and 4MeHA (80 and 70%, respectively). In contrast, the beta-ENDir response to 2TEA was totally blocked by Dx but only inhibited 50% by Br. The inhibitory effect of Dx on the beta-ENDir response to 2TEA was significantly stronger than the effect on the responses to HA and 4MeHA. POMC mRNA in the AL but not in the IL was increased almost 45% by HA and 2TEA and 20% by 4MeHA. Since all three histaminergic compounds in the doses used stimulated the release of beta-ENDir equipotently, the results indicate that H1-receptor activation predominantly affects the release and synthesis of beta-ENDir from the AL while H2-receptor activation affects the release of beta-ENDir equally from the two lobes and only to some extent increases the synthesis in the AL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1995

Dehydration stimulates hypothalamic gene expression of histamine synthesis enzyme: importance for neuroendocrine regulation of vasopressin and oxytocin secretion.

Dehydration associated with hyperosmolality and decreased extracellular volume stimulates arginine vasopressin (AVP) and oxytocin (OT) secretion from magnocellular neurons of the hypothalamus. The effects of hyperosmolality and decreased extracellular volume on the magnocellular neurons are mainly indirect and seem to be mediated centrally via several neurotransmitters and neuropeptides. Because histamine (HA), which serves as a central neurotransmitter, releases AVP and OT from the neurohypophysis when administered centrally, we investigated the possible role of HA in dehydration-induced AVP and OT secretion. To do this, we studied 1) the effect of dehydration on messenger RNA (mRNA) expression of the HA synthesis enzyme, histidine decarboxylase (HDC), in the tuberomammillary nucleus of the hypothalamus; and 2) the effect of HA synthesis inhibition during dehydration on AVP and OT mRNA expression in the supraoptic nucleus of the hypothalamus as well as on plasma AVP and OT levels. Forty-eight hours of dehydration increased the mRNA level of HDC in the tuberomammillary nuclei, whereas 24 h of dehydration had no effect. Pretreatment with the HA synthesis inhibitor alpha-fluoromethylhistidine (alpha FMH) increased the expression of HDC mRNA in 24-h dehydrated rats, but had no effect in euhydrated rats. In rats dehydrated for 48 h, the already increased level of HDC mRNA was not increased further by alpha FMH. Twenty-four and 48 h of dehydration increased AVP and OT mRNA levels in the supraoptic nucleus. This effect was inhibited by alpha FMH pretreatment. Dehydration increased the plasma levels of AVP and OT to an extent which depended on the duration of dehydration. Pretreatment with alpha FMH inhibited the hormone responses to 24 h of dehydration, but did not affect the responses to 48 h of dehydration. Twenty-four and 48 h of dehydration had no significant effect on the contents of AVP and OT in the neurohypophysis, whereas pretreatment with alpha FMH combined with 48 h of dehydration led to depletion of AVP stores in the neurohypophysis. Based on the present findings, we conclude that hypothalamic histaminergic neurons are involved in the regulation of dehydration-induced stimulation of magnocellular AVP and OT neurons.

Animals↗

PubMed1995

Beta-adrenergic receptors are involved in histamine-induced secretion of proopiomelanocortin-derived peptides and prolactin in rats.

The neurotransmitter histamine (HA) is involved in central regulation of secretion of prolactin (PRL) and the proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), beta-endorphin (beta-END) and alpha-melanocyte-stimulating hormone (alpha-MSH). The effect of HA on POMC-derived peptides and PRL release is, at least in part, indirect and may involve activation of catecholaminergic systems. Therefore, we investigated the effect of beta-adrenergic receptor blockade on HA or HA agonist-induced release of ACTH, beta-END, alpha-MSH and PRL. Central administration of HA, the H1-receptor agonist 2-thiazolylethylamine (2-TEA) or the H2-receptor agonist 4-methylhistamine (4-MeHA) stimulated the secretion of ACTH, beta-END, alpha-MSH and PRL. Pretreatment with the beta-adrenergic antagonist propranolol inhibited secretion of the POMC peptides in response to HA, 2-TEA or 4-MeHA. Propranonol only inhibited the PRL response to HA or 2-TEA, but had no effect on the PRL response to 4-MeHA. Administration of the beta-receptor agonist isoproterenol stimulated ACTH, beta-END, alpha-MSH and PRL two to five-fold. This effect was totally blocked by pretreatment with propranolol. We conclude that HA-induced secretion of POMC-derived peptides from the anterior and intermediate lobe of the pituitary gland and of PRL from the anterior lobe is, at least in part, mediated via catecholamines. beta-Adrenergic receptors are involved in the mediation of the POMC response to H1- as well as H2-receptor activation, whereas beta-receptors are involved only in the mediation of the PRL response to H1-receptor activation.

Adrenergic beta-Antagonists↗

PubMed1994

Role of hypothalamic histaminergic neurons in mediation of ACTH and beta-endorphin responses to LPS endotoxin in vivo.

The involvement of hypothalamic histaminergic neurons in the mediation of the ACTH and beta-endorphin (beta-END) response to lipopolysaccharide (LPS) endotoxin was investigated in conscious male rats. LPS stimulated the release of ACTH and beta-END dose-dependently and increased the hypothalamic concentration of the histamine (HA) metabolite tele-methylhistamine significantly and that of HA slightly, indicating an increased turnover of neuronal HA. Pretreatment with the HA synthesis inhibitor alpha-fluoromethyl-histidine administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) inhibited the ACTH and beta-END response to LPS about 60%, whereas i.p. administration of the H3 receptor agonist R(alpha)methylHA, which inhibits HA synthesis and release, decreased the response about 50%. Pretreatment with the H1 receptor antagonist mepyramine (67 micrograms x 2 i.c.v.) inhibited the hormone response to LPS about 50%, while pretreatment with equimolar doses of the H2 receptor antagonists cimetidine (67 micrograms x 2 i.c.v.) or ranitidine (83 micrograms x 2 i.c.v.) had no effect on the LPS-induced release of ACTH and beta-END. When the H1 receptor antagonists mepyramine and cetirizine were administered i.p. in doses (10 mg/kg) which penetrate the blood-brain barrier the hormone response to LPS was inhibited 50% and 30%, respectively. Administered i.p. the H2 receptor antagonists had no effect on the hormone response to LPS. We conclude that hypothalamic histaminergic neurons in rats are involved in the mediation of the ACTH and beta-END response to LPS stimulation via activation of central postsynaptic H1 receptors.

Adrenocorticotropic Hormone↗

PubMed1994

Histamine stimulates c-fos expression in hypothalamic vasopressin-, oxytocin-, and corticotropin-releasing hormone-containing neurons.

The stimulatory action of centrally administered histamine (HA) on secretion of the anterior pituitary hormones ACTH, beta-endorphin, and PRL is indirect, and previous studies have suggested that hypothalamic neurons containing CRH, arginine vasopressin (AVP), and oxytocin (OT) are involved in this response. We studied the effect of HA on neuronal activation in the hypothalamus by investigating the expression of c-fos, which is a protooncogene activated early when neurons are stimulated. The expression of c-fos was evaluated by detection of c-fos immunoreactivity (c-fos-IR) using immunohistochemistry and by measurement of c-fos mRNA using in situ hybridization techniques. In addition, the identity of the HA-stimulated neurons was investigated by dual antigen immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing increased c-fos expression. HA (270 nmol) infused intracerebroventricularly increased c-fos-IR in the hypothalamus, especially in the periventricular hypothalamic areas and certain hypothalamic nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON). c-fos-immunoreactive nuclei were observed throughout the SON, whereas in the PVN, c-fos-IR was particularly pronounced in the subnuclei known to contain AVP, OT, and CRH neurons. Double labeling experiments confirmed that c-fos was expressed in AVP-, OT-, and CRH-immunoreactive as well as other neurons. In addition, HA intracerebroventricularly induced a moderate expression of c-fos-IR in the arcuate nucleus. In situ hybridization showed increased levels of c-fos mRNA in both the PVN and SON after HA infusion. We conclude that HA-induced secretion of ACTH, beta-endorphin, and PRL may be mediated via activation of hypothalamic AVP, OT, and CRH neurons.

Animals↗

PubMed1994

Dehydration-induced release of vasopressin involves activation of hypothalamic histaminergic neurons.

The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.

Animals↗

PubMed1994

Histaminergic activation of the hypothalamic-pituitary-adrenal axis.

Centrally administered histamine (HA) stimulates the secretion of adenohypophysial POMC-derived peptides, which subsequently cause release of corticosterone. The effect of HA on POMC-derived peptide release is indirect, and it is possible that hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), or oxytocin (OT) are involved in the mediation of this response. We studied the effect of HA on: 1) expression of CRH, AVP, and OT messenger RNA (mRNA) at the hypothalamic level; 2) expression of c-fos and POMC mRNA at the pituitary level; and 3) peripheral plasma levels of AVP, OT, ACTH, beta-endorphin (beta-END), and corticosterone. HA (270 nmol) infused intracerebroventricularly increased the expression of CRH, AVP, and OT mRNA in the paraventricular nucleus as well as that of OT mRNA in the supraoptic nucleus of the hypothalamus. At the pituitary level the expression of mRNA for c-fos and POMC increased in the anterior but not in the intermediate lobe in response to HA. Plasma levels of AVP, OT, ACTH, beta-END, and corticosterone all increased in response to central HA administration. Circulating levels of AVP and OT peaked after 5 min, ACTH and beta-END after 15 min, whereas corticosterone levels were highest after 30 min. In concert with our earlier discoveries, the present data support the hypothesis that HA-induced secretion of ACTH and beta-END is mediated via central activation of hypothalamic neuroendocrine neurons containing CRH, AVP, and/or OT.

Animals↗

PubMed1994

Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors.

We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10-14-fold. Pretreatment with the selective V1-receptor antagonists [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-D-arginine]vasopressin or [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vassopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-D-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine-8-D-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1-antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stress-induced secretion of PRL, and that the AVP receptor involved is primarily of the V1-type or similar to this.

Animals↗