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PubMedDate not supplied

Effect of taurine on total parenteral nutrition-associated cholestasis.

A decrease in the formation/secretion of bile has been well documented in animals on total parenteral nutrition (TPN). Either an excess or an imbalance of amino acids (AA) has been most often implicated. In view of recent work showing that taurine promotes bile flow, bile acid secretion, and protects against hepatotoxic bile acids, the effect of adding taurine (15 mg/dL) to an AA solution was examined in guinea pigs on TPN for 3 days. The TPN-taurine group had a larger bile flow than the group without taurine and had bile acid secretory rates (BASR) similar to those of controls who were on saline by central catheter and had free access to food. Bile composition showed an increase in the secondary bile acid, 7-ketolithocholate and a concomitant decrease in chenodeoxycholate (CDC) in both experimental groups. Taurine led to a reversal of the usual predominance of glycine over taurine conjugated bile acids as well as to increases in HCO3 in cholesterol secretion. In response to a challenge with a large load of CDC, the TPN-taurine animals increased their BASR beyond those observed in the two other groups. These observations suggest that the addition of taurine to TPN solutions could play a role in the prevention of altered biliary function associated with AA solutions.

Amino Acids↗
PubMed1997

Regulation of depth and composition of airway surface liquid.

The depth and composition of human airway surface liquid (ASL) may depend on secretion from airway glands, ion transport across the surface epithelium, goblet cell discharge, transepithelial gradients in hydrostatic pressure, and surface tension. Published values for the frequency of airway glands and for the secretory rates of individual glands suggest that total gland secretion in human trachea can amount to approximately 60 microL x cm(-2) x h(-1). Volume absorption directly measured across cultures of surface epithelium from human trachea is approximately 5 microL x cm(-2) x h(-1). These flows should alter the depth of ASL at +10 and -1 microm x min(-1). We have looked for changes in ASL depth of this magnitude using low-temperature scanning electron microscopy (LT-SEM) of rapidly frozen specimens of bovine trachea. Stimulation of gland secretion with methacholine led to an initial increase in depth of approximately 25 microm x min(-1) followed by a decline at approximately 1.5 microm x min(-1). Whereas the initial increase in depth was probably due to transient gland secretion, the later decline reflected active absorption of liquid across the surface epithelium. Finally, we present preliminary data showing that LT-SEM can be combined with X-ray microanalysis to determine the elemental composition of ASL.

Adult↗
PubMed2003

Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans.

Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting. During a 10 h primed, constant infusion of 13C-valine (15 micromol/kg/h), enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL-1 and VLDL-2 by gas chromatography mass spectrometry. The synthesis rates of VLDL-1 apoB-100 and VLDL-2 apoB-100, catabolism, and transfer were estimated by compartmental analysis. Mean VLDL-1 apoB-100 pool size was 90 +/- 15 mg, and mean VLDL-2 apoB-100 pool size was 111 +/- 14 mg. Absolute synthesis rate of VLDL-1 apoB-100 was 649 +/- 127 mg/day and 353 +/- 59 mg/day for VLDL-2 apoB-100. There was a strong association between the absolute synthesis rate of VLDL-2 apoB-100 and L-C ratio (r 2 = 0.61, P < 0.01). In contrast, no correlation was observed between L-C ratio and absolute synthesis rate of VLDL-1 apoB-100 (r 2 = 0.302, P = 0.09). In conclusion, these data provide additional support for an independent regulation of VLDL-1 apoB-100 and VLDL-2 apoB-100 production. Endogenous cholesterol synthesis is correlated only with the VLDL-2 apoB-100 production.

Adult↗
PubMed1982

Mucin release from rabbit tracheal epithelium in response to sera from normal and cystic fibrosis subjects.

We have developed an assay for the release of mucous glycoproteins secreted by rabbit tracheal mucosa to study the mucus-stimulating properties of cystic fibrosis (CF) serum. Glycoproteins are labeled to equilibrium with both [35]-sulfate and [3H]-glucosamine. The relative secretory rate (RSR) of these glycoproteins is assessed after incubation with 50% (v/v) CF and control sera. Serum from all sources significantly increased the RSR for incubation times ranging from 10 min to 4 h. CF serum produced a significantly greater RSR than control serum after 10 min exposure, but not after longer exposure intervals. After 10 min, RSR for [35SO4]-glycoproteins was 3.6 +/- 0.2 in the presence of sera from healthy individuals, and 2.3 +/- 0.4 in the presence of sera from control patients with lung disease. Heterozygote RSR values were usually higher than control values, but not different than CF homozygote values. The CF serum activity was reduced by freezing and thawing. Increasing the calcium content of incubation medium did not alter serum effects. Calcium inophore A23187 did not mimic CF serum activity. High molecular weight and albumin, but not IgG, fractions from Sephadex G-200 chromatography of CF and control sera generally contained high levels of mucin-release activity. No chromatographic pattern of activity was distinctive for CF.

Adolescent↗
PubMed1987

Atrial natriuretic peptide in patent ductus arteriosus.

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in nine infants (age 4 days-9 months) before and after closure of patent ductus arteriosus. Initially all patients had marked distention of the left atrium as indicated by a left atrium to aortic root ratio greater than or equal to 1.3 on echocardiography. After closure of the ductus, operative in six and pharmacological in three patients, left atrial size normalized (left atrium to aortic root ratio less than 1.3) in all patients, except in one treated surgically. Before closure the plasma concentration of ANP was 86-2224 pg/ml and after closure 44-1400 pg/ml. There was a significant correlation between the size of left atrium and plasma concentration of ANP (r = 0.56; p = 0.01). Our results suggest that in infants with patent ductus arteriosus the left atrium is the main source of ANP. The secretory rate of ANP decreases immediately after restoring left atrial size by closure of the ductus.

Atrial Natriuretic Factor↗
PubMed2000

Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.

Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.

Aging↗
PubMed1981

Adrenocortical sensitivity to adrenocorticotropin (ACTH) in awake dogs changes as a function of the time of observation and after hemorrhage independently of changes in ACTH.

Adrenocortical sensitivity to ACTH, defined as the slope of the log dose-response curve, was determined in awake dogs by measuring cortisol secretory rates after graded doses of ACTH. Adrenocortical sensitivity varied as a function of the time of observation. The AM sensitivity was greater than the PM sensitivity in the absence of an AM-PM difference in basal plasma ACTH. Additionally, sensitivity was increased in the PM 6--8 h after moderate hemorrhage in the AM. However, exogenous ACTH given in the AM did not augment adrenal sensitivity to ACTH in the PM. These data show that adrenocortical sensitivity to ACTH varies in awake dogs and that the changes in sensitivity cannot be completely accounted for by changes in ACTH.

Adrenal Cortex↗
PubMed1984

Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids.

A paradigm for reliably stimulating ACTH secretion in urethane-anesthetized male rats has been used to examine hypothalamic secretion of corticotropin-releasing factor-like immunoreactivity (CRF-LI) into the hypophysial portal circulation. Hemorrhage of 15% estimated blood volume evoked a maximal 4.6-fold elevation in circulating ACTH levels from an initial level of 178.4 +/- 51.2 (+/-se) to 814.7 +/- 184.6 pg ml-1. The cumulative amount of ACTH secreted in response to hemorrhage was 10-fold greater than the cumulative amount of ACTH secreted by nonhemorrhaged rats (unweighted cumulative effect over all time points). In another experiment from a similarly hemorrhaged group, the hypophysial portal plasma CRF-LI concentration rose 2-fold from an initial level of 429.7 +/- 34.2 to 839.3 +/- 170.4 pg ml-1. Pretreatment with dexamethasone (100 microgram/kg BW, im) had no effect on initial levels of either CRF-LI or ACTH. The hemorrhage-induced elevations of both CRF-LI and ACTH were abolished in dexamethasone-treated rats. The secretory rate of CRF-LI was calculated to be 1.61 +/- 0.7 pg min-1 in nonhemorrhaged animals. Reversible pharmacological hyperpolarization of the paraventricular nuclei by stereotaxically microinjected procaine (15 micrograms/100 nl) reduced portal plasma CRF-LI and peripheral plasma ACTH to undetectable levels. These observations led to the following conclusions: 1) CRF-LI is an important hypothalamic regulator of adenohypophysial ACTH secretion, 2) CRF-LI in the hypophysial portal circulation is derived from CRF-LI-containing neurons within the paraventricular nuclei, and 3) glucocorticoid negative feedback effects can be exerted at the central level.

Adrenocorticotropic Hormone↗
PubMed1985

Corelease of dynorphin-like immunoreactivity, luteinizing hormone, and follicle-stimulating hormone from rat adenohypophysis in vitro.

Rat anterior pituitary quarters or acutely dispersed rat anterior pituitary cells were incubated in vitro, and the release of dynorphin A1-13-like immunoreactivity (Dyn A1-13-IR) into the incubation medium was studied. Addition of LHRH led to a concentration-dependent enhancement of the release of Dyn A1-13-IR with a maximum secretory rate which was about 4-fold higher than basal secretion. Dyn A1-13-IR was released by LHRH concomitantly with LH and FSH, and the concentration-response relationships as well as the time course were virtually identical. Gel filtration and HPLC revealed a single peak of Dyn A1-13-IR, with an apparent mol wt of about 6000. In addition to Dyn A1-13-IR, alpha-neo-endorphin-like immunoreactivity was released by LHRH. The LHRH-stimulated release of Dyn A1-13-IR was mimicked by the LHRH analog D-Ala6,des-Gly10-LHRH ethylamide and blocked in a competitive manner by the LHRH antagonist D-pGlu1,D-Phe2,D-Trp3,6-LHRH. Addition of TRH (5 microM), rat corticotropin-releasing factor (100 nM), arginine vasopressin (1 microM), or synthetic human pancreatic GH-releasing hormone (10 nM) produced no effect on Dyn A1-13-IR release. An extract of the rat medial basal hypothalamus stimulated the release of Dyn A1-13-IR and beta-endorphin-like immunoreactivity, and the former, but not the latter, effect was blocked by the LHRH antagonist D-pGlu1,D-Phe2,D-Trp3,6-LHRH. These results demonstrate that dynorphin-like material and other proenkephalin B-derived peptides are released concomitantly with LH and FSH from rat adenohypophysis in vitro upon activation of LHRH receptors. This may indicate that proenkephalin B-derived peptides coexist with LH and/or FSH in at least some gonadotrophs of the normal rat anterior pituitary gland.

Animals↗
PubMed1986

Nonsomatostatin secretory peptide(s) derived from prosomatostatin's amino terminus in a rat medullary thyroid carcinoma cell line.

We have established a system, the CA77 rat medullary thyroid carcinoma cell line, for studying the products of somatostatin (SS) gene expression. Based on the amino acid sequence of proSS, we developed a RIA for the amino terminus of proSS (proSS-NTP) and demonstrated in acidic cell extracts two major proSS-NTP-containing species of 8000 and 4000 daltons. Studies were then performed on species secreted into culture medium. Serial dilutions of culture medium showed tracer displacement curves parallel to serial dilutions of synthetic proSS-NTP standard. Analysis by gel filtration chromatography of 24-h culture medium showed the major proSS-NTP-containing species to have an estimated mol wt of 8000 daltons. No 4000-dalton species was observed. The acute effects of calcium and glucagon, known secretagogues of SS, on secretion of immunoreactive (i) proSS-NTP were investigated in 3-h experiments. Basal (0.5 mM calcium) secretory rates (mean +/- SE) of iproSS-NTP and iSS were 1.29 +/- 0.36 and 7.38 +/- 1.51 ng/mg acid-extractable protein, respectively. High calcium (3 mM) stimulated iproSS-NTP and iSS secretion 302 +/- 100% and 363 +/- 105%, respectively. High calcium plus 10(-6) M glucagon also stimulated secretion of iproSS-NTP and iSS in a coordinate fashion. Analyses by gel filtration chromatography of 3-h culture medium revealed that high calcium markedly increased the 8000-dalton proSS-NTP-containing species. No 4000-dalton species was observed. The absence of 4000-dalton proSS-NTP species in 24-h culture medium, the lack of degradation of 4000-dalton proSS-NTP (recovered from CA77 cell extracts) added to tissue culture medium, and the selective secretion of the 8000-dalton proSS-NTP species under both basal and stimulated conditions coordinate with the secretion of SS indicate that the 4000-dalton proSS-NTP-containing species is not secreted.

Animals↗
PubMed1987

Corticotropin-releasing factor in the dog adrenal medulla is secreted in response to hemorrhage.

To characterize the nature of CRF-like immunoreactivity (CRF-LI) in the dog adrenal, adrenal medullary, adrenal cortical, or hypothalamic tissue was extracted and subjected to RIA after partial purification on C-18 cartridges or Sephadex G-50. Using N- and C-terminal-directed antisera against rat/human (r/h) CRF, significant levels of CRF-LI were found in the adrenal medulla and hypothalamus, but not in the adrenal cortex. Immunocytochemical analysis revealed that CRF-immunoreactive cells were located in the adrenal medulla, many of them concentrated in the vicinity of blood vessels and at the border between adrenal medulla and cortex. However, the cortex was devoid of any CRF-positive cells. On reverse phase HPLC, CRF-LI in the adrenal medulla coeluted with synthetic r/hCRF. In a bioassay system, using dispersed rat anterior pituitary cells, purified adrenal CRF caused a dose-dependent increase in ACTH secretion parallel to the r/hCRF standard, indicating that dog adrenal medulla contains authentic r/hCRF. Evidence of CRF-LI secretion from the adrenal was supported by its presence in adrenal venous, but not in peripheral arterial, plasma. Adrenal venous plasma CRF-LI coeluted with r/hCRF on reverse phase HPLC after affinity chromatographic purification. The CRF-LI secretory rate in conscious trained dogs was 68 +/- 19 pg/min (concentration, 27 +/- 5 pg/ml). In response to 20% hemorrhage, the CRF-LI secretion rate rose 3-fold within 15 min and was associated with increased catecholamine secretion. The existence of a biologically active CRF-like substance in the dog adrenal medulla and its secretion in conjunction with catecholamines after a hemorrhage suggest a physiological role for this peptide other than pituitary or central nervous system regulation.

Adrenal Medulla↗
PubMed1988

Atrial natriuretic peptide inhibits the stimulation of aldosterone secretion but not the transient increase in intracellular free calcium concentration induced by angiotensin II addition.

The effect of atrial natriuretic peptide (ANP) on cellular calcium metabolism was evaluated in bovine adrenal glomerulosa cells stimulated by agonists that use the Ca2+-phosphoinositide messenger system. The calcium-sensitive probe aequorin was used to measure intracellular free calcium concentration, and the aldosterone secretory rate was simultaneously monitored. ANP did not block the calcium transient induced by beta-[Asp1]angiotensin II (beta-[Asp1]AII), an AII analog, but markedly reduced the stimulated rate of aldosterone secretion. Consistent with these findings, radiolabeled 45Ca efflux stimulated by AII and carbachol was not altered by the concurrent addition of ANP. These results indicate that ANP has no effect on the phosphoinositide-mediated calcium transient and the associated rise in cellular calcium efflux, suggesting that these parameters of calcium metabolism are not the locus of ANP's inhibitory action.

Aequorin↗
PubMed1988

Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin.

The cytosolic free calcium concentration and cumulative GH release were measured simultaneously in normal pituitary cells. This was made possible by a novel combination of fluorescence microscopy using the calcium indicator fura-2 and a reverse hemolytic plaque assay. GRF (10 nM) rapidly increased the intracellular free calcium concentration ([ Ca2+]i) from a basal level of 234 +/- 17 nM (mean +/- SE) to a peak value of 480 +/- 61 nM 1 min after stimulation. This GRF-induced calcium rise was totally abolished in calcium-free medium or in the presence of calcium channel blockers cobalt chloride (2 mM) and verapamil (100 microM). When somatostatin (SRIF; 1 nM) was added after basal recordings, cytosolic calcium decreased to 96 +/- 23 nM in identified somatotropes. [Ca2+]i returned to baseline upon the removal of SRIF inhibition. This rebound was higher when a sequential treatment of SRIF followed by GRF was applied. Exposing cells to a combination of GRF (10 nM) plus SRIF (1 nM) resulted in a decrease in [Ca2+]i identical to that caused by SRIF treatment alone. Despite the 10-fold excess of GRF, SRIF not only inhibited hormone secretion, but also totally overcame the GRF-induced rise of [Ca2+]i. In summary, stimulation by GRF increases cytosolic calcium in normal somatotropes. This increase is proposed to be due to the influx of calcium through membrane ion channels. In contrast, SRIF decreases [Ca2+]i. This might explain the cAMP-independent effects of this peptide. The effect of SRIF dominates over that of GRF with respect to both changes in [Ca2+]i and hormone release. Changes in the GH secretory rate are, therefore, accompanied by parallel changes in [Ca2+]i, both of which are primarily regulated by SRIF.

Animals↗
PubMed1989

Proadrenocorticotropin/endorphin production and messenger ribonucleic acid levels in primary intermediate pituitary cultures: effects of serum, isoproterenol, and dibutyryl adenosine 3',5'-monophosphate.

Long term primary rat intermediate pituitary cells cultured in complete serum-free medium (CSFM) were previously shown to exhibit a low basal secretory rate and maintain a stable cellular level of immunoactive pro-ACTH/endorphin (PAE)-related peptides. The present studies used biosynthetic labeling techniques to demonstrate that the biosynthesis of PAE-derived peptides declined as a function of the time the cultures were maintained in CSFM. Compared to hormone biosynthesis in freshly isolated cells, the ability of melanotropes maintained in CSFM to synthesize hormone declined approximately 3-fold after 5 days and 7-fold after 10 days. The endoproteolytic processing of PAE was not changed. This diminution in biosynthetic rate was not observed in serum-supplemented cultures; the rates of hormone secretion and hormone biosynthesis were both substantially higher in cultures maintained in serum-containing medium, suggesting that stimulatory factors were present in serum supplements. Chronic treatment of intermediate pituitary cultures in CSFM with 100 microM (Bu)2cAMP or 100 nM isoproterenol mimicked the effects of serum on total PAE production, hormone biosynthesis, and PAE mRNA levels. The diminished biosynthetic ability of cultures maintained in CSFM for several days could be restored by subsequent chronic (B mu)2cAMP or isoproterenol treatment. Taken together with previous information, these results suggest that melanotropes maintained in CSFM exist in a functionally basal state and that stimulatory agents, in addition to inhibitory inputs such as dopamine, exert significant regulatory control over intermediate pituitary lobe function in vivo.

Adrenocorticotropic Hormone↗
PubMed1989

Dissociation between changes in plasma bioactive and immunoreactive adrenocorticotropin after hemorrhage in awake dogs.

The secretion of cortisol increases in awake dogs after small hemorrhage, with little or no change in plasma immunoreactive (IR) ACTH. To determined if IR-ACTH reflects bioactive (B) ACTH after hemorrhage, changes in B-ACTH and IR-ACTH were determined in awake dogs. Trained dogs were prepared with adrenal venous and femoral arterial and venous cannula. Experiments performed 48-96 h after surgery consisted of blood sampling from the adrenal vein and femoral artery before and after a 7.5-10 ml/kg hemorrhage done over 3 min. Cortisol was assayed by HPLC with UV detection, and adrenal secretory rates were calculated using adrenal blood flow. Arterial B-ACTH was assayed after extraction using rat adrenal cells dispersed with collagenase; corticosterone produced was assayed by HPLC-UV. Arterial IR-ACTH was assayed by RIA using antisera directed against ACTH-(1-24). Dogs in which hypotension occurred (change in mean arterial pressure, -31 +/- 3; n = 6) were compared to dogs in which mean arterial pressure did not change (change in mean arterial pressure, -6 +/- 2; n = 5). In the absence of hypotension, B-ACTH increased by 10 min after the onset of hemorrhage coincident with increased cortisol secretion, whereas IR-ACTH did not increase until 20 min. Resting IR-ACTH was greater than B-ACTH (11 +/- 1 vs. 2 +/- 1 pg/ml), but the peak response of B-ACTH was greater than that of IR-ACTH (13 +/- 4 vs. 8 +/- 3 pg/ml). In the presence of hypotension, B-ACTH increased by 4 min, and IR-ACTH and cortisol secretion increased by 8 min after the onset of hemorrhage. Resting IR-ACTH was greater than B-ACTH (27 +/- 5 vs. 6 +/- 1 pg/ml), and the peak response of B-ACTH was less than that of IR-ACTH (64 +/- 26 vs. 112 +/- 33 pg/ml). In dogs subjected to blood sampling without hemorrhage (n = 4), resting IR-ACTH was greater than B-ACTH (34 +/- 5 vs. 5 +/- 1 pg/ml), but there was no change in B-ACTH, IR-ACTH, or cortisol secretion. The results show that small hemorrhage elicits changes in B-ACTH that are dissociated in time and magnitude from changes in IR-ACTH, are coincident with changes in cortisol secretion, and are greater in dogs that fail to maintain arterial pressure. These data indicate that B-ACTH predicts more accurately the change in cortisol secretion than does IR-ACTH after small hemorrhage.

Adrenal Cortex↗
PubMed1994

Blockade of alpha 2-adrenoceptors stimulates basal and stress-induced adrenocorticotropin secretion in the developing rat through a central mechanism independent from corticotropin-releasing factor and arginine vasopressin.

In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly reduced during the first 2 weeks of life [stress-hyporesponsive period (SHRP)]. In this report, we studied the effect of idazoxan (an alpha 2-adrenergic antagonist) on plasma ACTH and corticosterone levels in 8-day-old rats. Indeed, it is known that in the adult rat, blockade of alpha 2-adrenoceptors increases ACTH secretion stimulated by CRF and arginine vasopressin (AVP) injection. Injection of 2.5 micrograms/g idazoxan induced a rapid (within 30 min) increase in basal plasma ACTH and corticosterone levels that lasted for 60 min. Injection of increasing doses of idazoxan led to a dose-dependent stimulation of ACTH and corticosterone levels. Administration of 2.5 micrograms/g idazoxan significantly increased the ACTH response to insulin-induced hypoglycemia, whereas it potentiated and accelerated the ACTH response to ether exposure stress. We next examined ACTH secretion from superfused anterior pituitary glands. Neither the alpha 2-adrenergic agonist clonidine nor idazoxan changed the basal ACTH secretory rate. Idazoxan had no effect on CRF- and AVP-stimulated ACTH secretion. This indicates that in vivo, idazoxan acts at a suprapituitary level. To investigate a possible effect of idazoxan on presynaptic alpha 2-adrenoceptors, we studied the effect of idazoxan on the concentrations of norepinephrine (NE) and L-DOPA in punches of locus coeruleus after dopa-decarboxylase blockade. Idazoxan injection induced a decrease in the NE content, without changing L-DOPA levels, indicating that idazoxan can act at the level of presynaptic alpha 2-adrenoceptors, inducing an increased release and/or degradation of NE without any effect on catecholamines synthesis. Finally, we investigated a possible involvement of CRF and AVP in mediating the effect of alpha 2-adrenoceptor blockade on ACTH secretion. Passive immunization against CRF or AVP did not change the ACTH response to idazoxan administration, whereas idazoxan pretreatment had simply an additive effect on CRF- and lysine vasopressin-stimulated ACTH secretion. In conclusion, our data demonstrate that during the SHRP, blockade of alpha 2-adrenoceptors induces an increase in both basal and stress-induced ACTH secretion. They suggest that a decreased catecholaminergic tone, consecutive to an increased occupation of alpha 2-adrenoceptors, acting through a central mechanism independent from CRF and AVP may be responsible for the SHRP in the developing rat.

Adrenergic alpha-Antagonists↗