Biomedical subjects

Q J Pittman

Publications and source records attributed to Q J Pittman.

At least 55 records · Page 3Linked to original sources

PubMed1996

Peptidergic modulation of synaptic transmission in the parabrachial nucleus in vitro: importance of degradative enzymes in regulating synaptic efficacy.

This study examined the effects of substance P (SP) and calcitonin gene-related peptide (CGRP) on synaptic transmission in a pontine slice containing the parabrachial nucleus (PBN). Stimulation of the ventral, external lateral portion of the PBN elicited glutamate-mediated EPSCs in cells recorded using the nystatin perforated-patch recording technique in the external lateral, external medial, and central lateral subnuclei of the PBN. Bath application of SP or CGRP dose-dependently and reversibly attenuated the evoked EPSC. The attenuation of the EPSC induced by both of these peptides was not accompanied by changes in input resistance of PBN cells over a wide voltage range, nor did these peptides alter the inward current induced by a brief bath application of AMPA. The combined application of subthreshold concentrations of these peptides revealed a synergistic interaction in reducing the evoked EPSC. The substance P neurokinin-1 receptor antagonist CGP49823 completely and reversibly blocked both the SP- and the CGRP-induced attenuation of the EPSC. However, the rat CGRP receptor antagonist human-CGRP8-37 did not block the actions of CGRP or SP on the EPSC. Using a metabolically stable analog of SP, SP (5-11), or an endopeptidase inhibitor, phosphoramidon, we were able to demonstrate that CGRP enhances the SP effect by inhibiting an SP endopeptidase. Application of phosphoramidon also revealed an endogenous SP "tone" apparently made effective by blockade of the endopeptidase. These results suggest that SP (and CGRP indirectly through an inhibition of the SP endopeptidase) acts on presynaptic NK-1 receptors to cause an inhibition of excitatory transmission in the PBN. These results indicate an important role of endopeptidases in regulating synaptic modulation by peptides.

Animals↗

PubMed1996

Oxytocin released within the supraoptic nucleus of the rat brain by positive feedback action is involved in parturition-related events.

Oxytocin is released within the supraoptic nucleus during parturition and suckling. During suckling, such release is important in positive feedback stimulation of oxytocin neurons. We have investigated whether oxytocin released within this hypothalamic nucleus during parturition (1) acts on local receptors to further amplify its own release in a positive feedback manner and (2) is critically involved in the regulation of the delivery process. To examine the effect of the oxytocin antagonist on oxytocin release within the supraoptic nucleus, microdialysates were sampled before and during parturition and either vehicle or the antagonist was infused adjacent to the microdialysis probe directly into the supraoptic nucleus after delivery of the second pup. Intranuclear infusion of an oxytocin receptor antagonist (des-Gly-NH2d(CH2)5[Tyr(Me)2Thr4]OVT; 50 ng/0.5 microliters) significantly (P < 0.01) diminished the parturition-related rise in oxytocin release within the supraoptic nucleus and reduced the number of pups delivered during the first and second 30-min dialysis period compared to vehicle-treated controls. Bilateral infusion of the oxytocin receptor antagonist into the supraoptic nucleus after delivery of the second pup significantly slowed parturition (P < 0.05), although the parturition-related rise in plasma oxytocin concentration was unchanged. In addition, the onset of suckling was significantly affected by the antagonist as indicated by fewer liver pups and fewer surviving pups with milk in their stomachs 24 hours after parturition (P < 0.05). To seek other, periventricular sites of oxytocin action during parturition, oxytocin or the oxytocin antagonist was infused into the lateral cerebral ventricle from the birth of pup 2. Via this route, oxytocin speeded up parturition, but the antagonist was ineffective; thus it appears that periventricular oxytocin-sensitive sites are not normally active in promoting parturition, and can do so. The findings indicate a receptor-mediated positive feedback action of oxytocin on its own release within the supraoptic nucleus during parturition, which seems to be involved in the progress of parturition without significantly affecting circulation oxytocin levels. Oxytocin released within the supraoptic nucleus might be important for the coordinated activation of oxytocin neurons and for the synergistic central and peripheral oxytocin effects involved in the regulation of parturition-related events necessary for the survival of the newborn, including the onset of lactation.

Animals↗

PubMed1996

Prostaglandin fever in rats throughout the estrous cycle late pregnancy and post parturition.

We have examined the influence of natural variations in endocrine status on the ability to generate a prostaglandin-induced fever in virgin female, pregnant and lactating rats and compared responses to those in male rats. Endocrine status of virgin female rats was assessed from examination of vaginal smears and time of parturition noted to enable accurate dating of pre- and postparturient fevers. Unanesthetized rats, previously prepared with intraventricular guide cannulas and intraperitoneal telemetry thermistors, were given intraventricular injections of prostaglandin E1 (2-100 ng/5 microliters) and temperatures monitored for 3 h after injection. Virgin females developed significantly larger fevers than did males at higher doses. There were no significant alterations in either fever height or duration as a function of the phase of the reproductive cycle in the females. Both pregnant and postparturient rats within the several days around birth displayed significantly lower fevers than did virgin females, but there was no further reduction in the immediate periparturient period. These data indicate that there are sex-, and possibly hormone-dependent differences in the central mechanisms involved in fever generation and antipyresis.

Alprostadil↗

PubMed1996

GABAB receptors presynaptically modulate excitatory synaptic transmission in the rat supraoptic nucleus in vitro.

1. The effect of gamma-aminobutyric acid-B (GABAB)-receptor activation on excitatory synaptic transmission in the rat supraoptic nucleus (SON) was examined using the nystatin perforated-patch whole cell recording technique in coronal hypothalamic slices. 2. Stimulation of the hypothalamic region dorso-medial to the SON elicited glutamate and GABAA-receptor-mediated synaptic responses in electrophysiologically identified magnocellular neurosecretory cells. 3. Bath application of the GABAB-receptor agonist, +/- -baclofen reversibly reduced pharmacologically isolated, glutamate-mediated excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner. At the concentrations used, baclofen altered neither the postsynaptic conductances of these cells nor their response to bath applied alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. The baclofen-induced synaptic depression was accompanied by an increase in paired pulse facilitation (PPF). This increase in PPF, as well as the synaptic depression, was blocked by the GABAB-receptor antagonists CGP36742 and saclofen. 5. In addition to blocking the actions of baclofen in this nucleus, CGP36742 caused an increase in the evoked EPSC amplitude without altering postsynaptic cell conductances or responses induced by bath-applied AMPA. Contrary to the action of CGP36742, saclofen caused a baclofen-like depression of the evoked EPSC, suggesting that it may act as a partial GABAB receptor agonist. 6. These results indicate that the activation of presynaptic GABAB receptors reduces fast excitatory synaptic transmission in the SON. They further suggest that presynaptic GABAB receptors may be tonically activated in vitro. Thus GABAB receptors may influence the level of activity and excitation of SON neurons and hence modulate the secretion of the regulatory neuropeptides vasopressin and oxytocin.

Animals↗

PubMed1995

Vasopressin-induced sensitization: involvement of neurohypophyseal peptide receptors.

Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasopressin analogs, including deamino-D-vasopressin, [pGlu4,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH9(2)-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)1(5),Tyr(Me)2]vasopressin, but not the vasopressin V2 receptor antagonist, [d(CH2)1(5),Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)1(5),D-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]vasotocin ([d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next, we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.

Amino Acid Sequence↗

PubMed1995

Interleukin-1 beta stimulates both central and peripheral release of vasopressin and oxytocin in the rat.

Simultaneous microdialysis in the brain and blood was used to monitor the release of vasopressin and oxytocin within the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei and into the systemic circulation of urethane-anaesthetized male rats before and after central administration of interleukin-1 beta (IL-1 beta). Following intracerebroventricular infusion of the cytokine (200 ng/5 microliters), the content of vasopressin (up to 278% compared to vehicle-treated control, P < 0.01 compared to vehicle-treated control and preinfusion baseline) but not oxytocin (up to 148%, not significant) in 30-min blood microdialysates was found to be increased. This peripheral release was accompanied by a transient rise in vasopressin (up to 163%, P < 0.05) and oxytocin (up to 182%, P < 0.05) release within the SON, the peak typically occurring during the first and second 30-min collection intervals after IL-1 beta respectively. In contrast, in the simultaneously microdialysed PVN, both vasopressin and oxytocin failed to respond to intracerebroventricular IL-1 beta. In another series of experiments, IL-1 beta was directly infused (20 ng/0.5 microliters) into either the SON or PVN during microdialysis of the corresponding nucleus. The cytokine caused a significant and immediate rise in intra-SON release of both vasopressin (up to 225%, P < 0.01) and oxytocin (up to 178%, P < 0.05). Again, in the PVN, nonapeptide release, although tending to be stimulated in response to intranuclear IL-1 beta, failed to reach statistical significance. The cytokine-induced central and peripheral release pattern appeared to be independent of the rise in body temperature observed after IL-1 beta administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Involvement of the PVN and BST in 1K1C hypertension in the rat.

The paraventricular nucleus of the hypothalamus (PVN) and the bed nucleus of the stria terminalis (BST) are two sources of central nervous system (CNS)-derived arginine vasopressin (AVP), a nonapeptide that has been implicated in central autonomic regulation and in particular in cardiovascular regulation, through its actions within the CNS. These experiments were designed to determine if either the PVN or the BST were involved in the development of Goldblatt one-kidney one-clip (1K1C) hypertension in the rat. In order to test this hypothesis, ibotenic acid lesions of the PVN or electrolytic lesions of the BST were undertaken in both normotensive (sham-operated) rats and in 1K1C rats. In both cases the development of 1K1C hypertension was inhibited over the 18-21 days following surgery. Lesions of the PVN did not alter normal blood pressure regulation in the sham-operated animals, whereas lesions to the BST did affect normal blood pressure regulation, resulting in a dramatic increase in blood pressure during the initial days following surgery. These studies suggest that the PVN and BST are involved in the development of 1K1C hypertension in the rat, moreover the BST may also play a role in central cardiovascular control.

Animals↗

PubMed1995

Nitric oxide-releasing NSAIDs: a novel class of GI-sparing anti-inflammatory drugs.

The addition of a nitric oxide-releasing moiety to a number of common nonsteroidal anti-inflammatory drugs markedly reduces their toxicity in the gastrointestinal tract without interfering with their ability to inhibit prostaglandin synthesis. Moreover, the anti-inflammatory and anti-pyretic activities of the nitric-oxide releasing NSAID were comparable to the parent compound, while the anti-thrombotic activity in vivo was significantly enhanced. Nitric oxide-releasing NSAIDs may represent an alternative to existing anti-inflammatory, anti-pyretic and anti-thrombotic agents with greatly reduced toxicity in the gastrointestinal tract.

Analgesics, Non-Narcotic↗

PubMed1995

Changes in arterial blood pressure alter activity of electrophysiologically identified single units of the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis may play a role in cardiovascular function by way of its connectivity to the diagonal band of Broca/ventral septal area. The present study sought to determine whether changes in systemic blood pressure affect the electrical activity of single units within the bed nucleus of the stria terminalis. Extracellular voltage recordings from neurons in the bed nucleus were performed in urethane-anaesthetized rats catheterized for arterial blood pressure measurements and for the intravenous administration of pressor and depressor drugs. Afferent or efferent connectivity of each recorded neuron was determined following electrical stimulation of nearby nuclei with and without known barosensitive regions. Of neurons demonstrating efferent connectivity (antidromically evoked potentials) with the diagonal band of Broca/ventral septal area or habenular nuclei, 24 and 20%, respectively, responded to changes in blood pressure with either increases or decreases in firing frequency. Paraventricular nucleus-projecting neurons were not affected by alterations in arterial blood pressure. Orthodromic potentials (inhibitory and/or excitatory) in the bed nucleus were also observed following stimulation of these nearby nuclei. Of these orthodromically activated neurons, changes in arterial pressure affected 31% of neurons receiving input from the diagonal band of Broca/ventral septal area, 33% of neurons with connectivity to the habenular nuclei and 60% of neurons with connectivity to the paraventricular nucleus. These data show that the bed nucleus of the stria terminalis contains a sub-population of cells that are sensitive to deviations in resting arterial pressure and that these cells receive synaptic modulation from several limbic/forebrain sources. Furthermore, the results are consistent with a role for the bed nucleus in the control of cardiovascular function and as a relay nucleus for modified baroreceptor input toward the diagonal band of Broca/ventral septal area.

Animals↗

PubMed1995

Responses of electrophysiologically identified rat paraventricular neurons to cholecystokinin and other stimuli.

Extracellular recordings were carried out in the paraventricular nucleus of halothane-anesthetized male rats. Responses of neurons identified by antidromic criteria with projections to the nucleus tractus solitarius or to the ventral lateral medulla were compared to those of neurohypophysial neurons following alterations in blood pressure and osmolarity, hemorrhage and after intravenous injection of cholecystokinin. Neurohypophysial neurons displayed the well-described responses to blood pressure for putative vasopressin neurons and increases in excitability after cholecystokinin for putative oxytocin neurons. Twenty per cent of the ventral lateral medulla-projecting neurons were responsive to cardiovascular perturbations, with these displaying reduced activity after either decreases or increases in blood pressure. None of nine neurons projecting to the ventral lateral medulla responded to i.v. cholecystokinin. Two of 20 nucleus tractus solitarius-projecting neurons showed reduced activity after cholecystokinin and none increased their firing rate. Nitroprusside-induced hypotension was associated with reduced activity in 10% of this population. Three neurons displayed axon projections to both pituitary and medulla; two of these which projected to the nucleus tractus solitarius were activated by cholecystokinin. We conclude that some of the paraventricular nucleus neurons projecting to the medulla respond to recognized cardiovascular stimuli for neurohypophysial neurons, but neurons in these populations are generally unresponsive to cholecystokinin. The former group of neurons may act to coordinate autonomic and endocrine responses to cardiovascular perturbation; however, there may be other stimuli, such as cholecystokinin, which act only on one of the populations of paraventricular nucleus neurons. Furthermore, many neurons in the descending pathways may respond to stimuli not presently associated with activation of magnocellular neurons.

Action Potentials↗

PubMed1995

Acute, sequence-specific effects of oxytocin and vasopressin antisense oligonucleotides on neuronal responses.

Antisense oligodeoxynucleotides (antisense) are short length single strands of DNA with base sequences complementary to a length of messenger RNA of a specific gene. They can be taken up by neurons and hybridize with a complementary messenger RNA to selectively interrupt the expression of a particular gene. We now describe neuropeptide-specific, short-latency (within 2-6 h) effects of antisense infused into the supraoptic nucleus on the responses of rat neurohypophysical neurons, in vivo, to various stimuli. Oxytocin antisense specifically (i) reduced the electrophysiological responses of putative oxytocin, but not vasopressin neurons, (ii) inhibited cholecystokinin-induced and electrically stimulated release of oxytocin from the neurohypophysis, and (iii) reversibly abolished cholecystokinin-induced expression of Fos within the supraoptic nucleus. Vasopressin antisense reduced the excitatory responses of vasopressin neurons, but not of oxytocin neurons. As neuropeptide content within the supraoptic nucleus and neurohypophysis remains unaltered at this time, antisense may induce anticipatory, feed-forward alterations in electrical activity in addition to any possible effects on peptide synthesis.

Animals↗

PubMed1995

Microdialysis with high NaCl causes central release of amino acids and dopamine.

Recent studies have shown that the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) are released within the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus in response to microdialysis of these nuclei with high-NaCl perfusion media. These results suggest an inherent osmosensitivity of SON and PVN neurons. To investigate whether the observed release of AVP/OXT is a unique phenomenon to these neuropeptides, several brain regions were examined for the release of amino acids or dopamine in response to high- or low-NaCl stimulation. Urethane-anesthetized male Sprague-Dawley rats were perfused with five-ion solution using U-shaped microdialysis probes. Samples were collected at 30-min intervals and analyzed for amino acids and dopamine by HPLC. In the dialysates of all perfusion areas, including the SON, PVN, hippocampus, and striatum, concentrations of Asp, Glu, Ser, Gln, Gly, taurine (Tau), and gamma-aminobutyric acid (GABA) were significantly increased during perfusion with high-NaCl medium. This release was found to be dose dependent when tested in the hippocampus and striatum with perfusion medium containing 0.5 or 1.0 M NaCl. However, only the release of Glu and Ser was found to be Ca2+ dependent. In contrast, the use of mannitol, a nonionic osmolyte, for perfusions in the striatum in concentrations of 0.5 and 1 M resulted in reduced levels of amino acids in the dialysates (Glu, Ser, Gln, and Tau). Low-NaCl perfusion medium (0.01 M) resulted in significantly increased Glu, Tau, Gly, and GABA levels in the striatum. In addition, dopamine levels in striatal dialysates were significantly increased during stimulation with 1 M NaCl. These results indicate that stimulation with high NaCl concentrations affects the release of several neurotransmitters and is not specific for AVP and OXT. The described phenomenon of the release of amino acids in response to this stimulation seems to be a response to the changed ionic concentration rather than to the osmolality. In light of these findings shown for amino acids and dopamine as well as those previously reported for AVP, OXT, and angiotensin, it would appear that sensitivity to tonicity changes brought about by microdialysis may be a feature of many transmitter systems.

Amino Acids↗

PubMed1995

Fever in pregnant, parturient, and lactating rats.

Conscious virgin, pregnant, or lactating rats were given intravenous Escherichia coli endotoxin while their temperatures were monitored telemetrically. Virgin females responded to 10-50 micrograms/kg endotoxin with a slight hypothermia, followed by a fever of nearly 2 degrees C magnitude. In pregnant rats given 25 micrograms/kg of the endotoxin, fevers were reduced between 96 h before and 24 h after parturition compared with those seen in virgins or in lactating rats > 24 h postpartum. In the 24-h period before expected time of parturition, no rat developed a fever and the majority of animals became hypothermic; furthermore, in 80% of such animals given 25 micrograms/kg endotoxin, the hypothermia was accompanied by death within 3-15 h. Some mortality and hypothermia were also seen up to 48 h before birth and up to 24 h after birth. No mortality was observed in virgin, pregnant, or lactating rats outside of this time period. We conclude that, around the time of delivery, there is a suppression of fever in the rat and occasional toxic responses to endotoxin.

Animals↗

PubMed1995

Fundus striati vasopressin receptors in blood pressure control.

Vasopressin (VP), given intracerebrally to rats, can induce antipyresis, motor disturbances, and increases in arterial blood pressure. The possibility that the VP-binding sites in the fundus striati (FStr) could participate in these effects was investigated. After a bilateral injection of 100 pmol of VP into the FStr, the fever induced by an injection of the lipopolysaccharide of Escherichia coli (50 micrograms/kg ip) was not affected. Bilateral injections of 100 pmol of VP did not induce motor disturbances or alterations in body temperature after either of two successive injections. In contrast, bilateral injections of VP into urethan-anesthetized rats induced dose-dependent increases in arterial pressure without affecting heart rate. This increase was blocked by a V1 antagonist; oxytocin and a V2 agonist were ineffective. In keeping with this preliminary pharmacological analysis, radio-ligand-binding studies of the FStr revealed binding sites in the FStr exhibiting a binding profile typical of the V1 subtype. This study suggests that the V1 receptors in the FStr could participate in the central regulation of the blood pressure.

Animals↗

PubMed1995

Osmotic responsiveness and cross talk involving oxytocin, but not vasopressin or amino acids, between the supraoptic nuclei in virgin and lactating rats.

Lactation is associated with complex changes of the hypothalamo-neurohypophysial system, and oxytocin released within the hypothalamic supraoptic (SON) and paraventricular nuclei may serve as a signal of communication between the magnocellular nuclei in lactating rats. In the first study, the intranuclear and peripheral release patterns of oxytocin and vasopressin in response to intraperitoneal hypertonic saline were studied in virgin and lactating rats to determine if the reduced osmoresponsiveness of the oxytocinergic and vasopressinergic systems during lactation is reflected by reduced release not only into blood, but also within the SON. Simultaneous microdialysis was performed within the SON and the jugular vein before and up to 6 hr after peripheral osmotic stimulation (3.0 M NaCl, 0.6 ml/100 gm body weight, i.p.). There was an immediate increase in secretion of both oxytocin and vasopressin into blood, whereas peptide release within the SON was delayed and peaked after 4-5 hr. Peripheral release of both peptides was significantly reduced in lactating animals, whereas within the SON release of oxytocin, but not vasopressin, was significantly reduced during lactation. In the second study, cross talk between the SONs--another phenomenon which seems to be characteristic for lactation--was studied. Microdialysis of one SON with hypertonic perfusion medium (with 1 M NaCl) significantly increased the release of oxytocin, vasopressin, and various amino acids (aspartate, glutamate, serine, glutamine, gamma amino butyric acid, and arginine) within the ipsilateral SON. In contrast to virgin female and male animals, this unilateral stimulation of the SON resulted in a transiently increased release of oxytocin in the contralateral SON of lactating rats. The release of vasopressin and amino acids within the contralateral SON of lactating rats remained unchanged, indicating specific activation of contralateral oxytocinergic neurons.

Amino Acids↗

PubMed1995

Release of oxytocin within the supraoptic nucleus. Mechanisms, physiological significance and antisense targeting.

In addition to its secretion from neurohypophysial terminals, oxytocin (OT) is released within the hypothalamic magnocellular nuclei--the supraoptic (SON) and paraventricular nuclei--in response to various stimuli as mainly shown by microdialysis studies. During parturition and suckling, OT is released within the SON in a positive feedback role to further amplify its own local and/or neurohypophysial release depending upon the reproductive conditions. Whereas, for instance, intra-SON OT is important for appropriate OT secretion and milk ejection during suckling, it seems to be involved in the timing of the parturition process without directly affecting OT secretion during birth. As a consequence of various morphological and physiological adaptations of the OT system during lactation, the release pattern of OT into blood and within the SON is altered in response to other stimuli, like swim stress and peripheral osmotic stimulation. In addition, in lactating, but not virgin female or male rats, unilateral stimulation of the SON results in the release of OT, but not vasopressin or various amino acids, within the contralateral SON, which implicates a functional role of intranuclear OT in the plastic coupling of the paired SON during lactation. To manipulate OT synthesis and release, antisense targeting was used. Novel, acute effects (within 5 hours) of an OT antisense oligodeoxynucleotide on suckling-related parameters and, specifically, on the electrophysiological excitability of OT neurons as well as their ability to express the Fos-protein after CCK-8 are described. Since the OT content in the hypothalamo-neurohypophysial system was still unaffected at this time, antisense oligonucleotides may induce feedforward alterations in neuronal responsiveness which precede or parallel effects on neuropeptide synthesis. Taken together, the functional significance of OT released within the brain and into blood during reproduction provides an example of how a neuropeptide might regulate complex physiological and behavioral performances in a synergistic manner.

Adaptation, Physiological↗

PubMed1994

Central interleukin-1 beta stimulation of vasopressin release into the rat brain: activation of an antipyretic pathway.

1. Arg8-vasopressin (AVP)-containing neurones of the bed nucleus of the stria terminalis (BST), which terminate in the ventral septal area (VSA) of the rat brain, provide a pathway which controls body temperature during fever. The present study was conducted to test the hypothesis that interleukin-1 beta (IL-1 beta) may trigger the antipyretic response by evoking AVP release from BST neurones projecting into the VSA. 2. The push-pull perfusion technique and radioimmunoassay were utilized to determine the AVP concentrations of retrieved VSA perfusion fluid in urethane-anaesthetized rats following BST infusion of vehicle or IL-1 beta (125 or 500 pg (2 microliters)-1). 3. Ventral septal AVP levels significantly increased from basal levels, in a dose-related manner, in response to IL-1 beta (0-500 pg). Electrical stimulation of the same areas of the BST also evoked AVP release into the VSA. 4. IL-1 beta infusions and electrical stimulation of the BST resulted in significant increases in rectal temperature. In IL-1 beta-treated animals (500 pg), the change in body temperature and VSA AVP release were negatively correlated (P < 0.001). However, external heating of the animals to approximately the same levels as electrically stimulated or IL-1 beta treated rats did not affect basal AVP release. 5. These data show that IL-1 beta is a potent stimulus for AVP release from BST neurones and supports BST involvement in neuro-immune interactions. We propose, that in addition to febrogenesis, IL-1 beta is also a key component in the process of endogenous antipyresis by activating vasopressinergic BST neurones to release AVP during fever.

Animals↗

PubMed1994

Lack of fever suppression or central AVP release in 1K1C hypertensive rats.

Previous studies from our laboratory showed a transient suppression of the febrile response to intracerebroventricular (i.c.v.) PGE1 in the one-kidney, one-clip (1K1C) model of hypertension. This may have been due to an enhanced vasopressinergic transmission since arginine vasopressin (AVP), acting within the central nervous system (CNS), is thought to mediate endogenous antipyresis. These initial experiments utilized a protocol for the induction of 1K1C hypertension which produced an initial rapid rise in blood pressure, evident by day 4 following surgery, with a corresponding inhibition of the febrile response. The present experiments utilized a more slowly developing 1K1C hypertension (evident by day 12 following surgery) to firstly attempt to determine if inhibition of the febrile response is due to the actual change in blood pressure or to neural signals arising from the clipped kidney, and secondly to determine if the concentration of AVP in push-pull perfusates of the ventral septal area (VSA) of pyrogen-treated sham-operated and 1K1C rats were altered. In urethane-anaesthetized rats, i.c.v. PGE2 evoked brisk monophasic fevers in both 1K1C and sham-operated animals, with no significant difference between fever heights. Consistent with this, we found no increase in immunoreactive AVP from perfusates of the VSA of 1K1C rats. These results suggest that there is no inhibition of the febrile response to PGE2 when a slower developing hypertension is induced, nor is there an elevated release of AVP into the VSA under our conditions. We conclude that a rapid increase in blood pressure, and not high blood pressure per se, is required to produce an inhibition of the febrile response.

Alprostadil↗