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Q J Pittman

Publications and source records attributed to Q J Pittman.

At least 73 records · Page 4Linked to original sources
PubMed1994

Alteration of the physiological responses to indomethacin by endotoxin tolerance in the rat: a possible role for central vasopressin.

1. Previous studies suggest that arginine vasopressin (AVP) is released into the ventral septal area (VSA) of the rat brain during the antipyresis induced by the cyclo-oxygenase inhibitor indomethacin. In addition, there is evidence for increased AVP transmission in the VSA of animals having a reduced pyretic response following three intravenous injections of bacterial endotoxin (LPS) (endotoxin tolerant). Since ventral septal AVP receptors can also become 'sensitized' following exposure to AVP, we questioned whether the antipyretic action of indomethacin would increase, via an action involving central AVP, if this drug were administered into LPS-tolerant rats. 2. Intraperitoneal indomethacin (7.5 mg kg-1) was effectively antipyretic when administered 2 h after an intravenous challenge with LPS (50 micrograms kg-1) into conscious unrestrained rats. This dose of indomethacin had no effect on the core temperature of non-febrile rats given intravenous 0.9% pyrogen-free saline. 3. Three intravenous injections of LPS over a period of 3 days resulted in rats that were tolerant to the pyrogenic effects of LPS. When indomethacin was administered 2 h following the third LPS injection, a dose-dependent hypothermia was observed. This effect was age dependent, as profound hypothermia was seen in 8 week but not 20 week old rats. 4. A mortality rate of 41% (P = 0.02) was observed within 24 h of indomethacin treatment in 8 week old tolerant rats compared with 0% in 8 week old non-tolerant and 20 week old tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Effect of potassium-induced cortical spreading depression on prostaglandin-induced fever in conscious and urethane-anesthetized rats.

Potassium-induced cortical spreading depression (CSD) on prostaglandin E1 (PGE1) induced fever has been investigated in a dose-responsive experimental design in both conscious and urethane-anesthetized adult male Sprague-Dawley rats. While CSD in itself had no effect on nonfebrile body temperature even under cold ambient conditions, CSD significantly suppressed small but not large fevers induced by intracerebroventricular PGE1. The increased oxygen consumption during fever was also reduced. We also explored the possible involvement of the antipyretic peptide arginine vasopressin, in the CSD-induced suppression of fever. Long term castrated rats have significantly reduced ventral septal levels of this peptide, yet CSD was effective in suppressing the initial 40 min of PGE1 fever in these animals. Thus we conclude that increased release of ventral septal arginine vasopressin is probably not involved in the action of CSD on fever.

Anesthesia↗
PubMed1994

Nitric oxide actions in paraventricular nucleus: cardiovascular and neurochemical implications.

We have examined potential functions of nitric oxide (NO) within the paraventricular nucleus (PVN) in urethan-anesthetized male Sprague-Dawley rats. Initial experiments demonstrated microinjection of 50 pmol of the NO donor, sodium nitroprusside (SNP), directly into the PVN resulted in significant decreases in mean blood pressure (BP) (-3,312 +/- 1,189 mmHg/s over 300-s response time; P < 0.05). To determine whether such effects were attributable to SNP-induced NO release, NO was administered into PVN directly by bilateral microdialysis of NO-containing artificial cerebrospinal fluid (NO-aCSF), a process that results in delivery of approximately 50 pmol NO.PVN-1 x min-1. Such microdialysis resulted in significant decreases in BP (-5,121 +/- 817 mmHg/s over 1,200-s response time; P < 0.005), while aCSF microdialysis was without effect (1,298 +/- 1,071 mmHg/s over 1,200-s response time; P > 0.1). Amino acid concentrations were measured in dialysates collected during perfusion of the same PVN sites with either aCSF or NO-aCSF by high-performance liquid chromatography (HPLC) analysis. NO-aCSF induced significant increases in aspartate (aCSF 31 +/- 7 pmol/30 min; NO-aCSF 134 +/- 33 pmol/30 min; P < 0.05), glutamate (aCSF 36 +/- 5 pmol/30 min; NO-aCSF 417 +/- 108 pmol/30 min; P < 0.02), gamma-aminobutyric acid (aCSF 4.1 +/- 0.7 pmol/30 min; NO-aCSF 104 +/- 29 pmol/30 min; P < 0.02), and taurine (aCSF 34 +/- 3 pmol/30 min; NO-aCSF 117 +/- 24 pmol/30 min; P < 0.01) concentrations, while alanine, glutamine, and serine concentrations were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Enhanced pressor responses to ICV vasopressin after pretreatment with oxytocin.

The role of oxytocin (OT) in the modulation of arginine vasopressin (AVP)-induced cardiovascular effects within the central nervous system was investigated in urethan-anesthetized rats. Intracerebroventricular injection of AVP (1-10 pmol) produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR). These responses were enhanced in rats pretreated 24 h earlier with OT (10 pmol icv). The enhanced cardiovascular effects of AVP in OT-pretreated animals were dose dependent, blocked by the V1 antagonist d(CH2)5Tyr(Me)AVP, not evoked by OT alone, and occurred in the absence of changes in basal (nonstimulated) MAP and HR. In addition, central administration of AVP in OT-pretreated rats, but not in saline-pretreated controls, caused dose-dependent oscillations of the MAP and HR responses and, at higher doses, death of the animals. The enhanced cardiovascular actions of centrally injected AVP in OT-pretreated rats do not appear to be secondary to skeletal muscle contractions or the result of cerebral ischemia. Our data point to an interaction between the central oxytocinergic and vasopressinergic systems in cardiovascular control.

Animals↗
PubMed1994

Reduced febrile responses to pyrogens after lesions of the hypothalamic paraventricular nucleus.

The hypothalamic paraventricular nucleus (PVN) is recognized as a major site of autonomic control, but the role of this nucleus in thermoregulation is unclear. Therefore the role of the PVN in the febrile response and in the maintenance of normal body temperature was investigated. Conscious, unrestrained rats with chronic lesions of the PVN received intracerebroventricular injections of several doses of prostaglandin (PG) E2 or intraperitoneal applications of Escherichia coli lipopolysaccharide. The body temperatures of both lesioned and sham-operated animals, monitored via radio telemetry, were compared. Intracerebroventricular PGE2 at doses of 10, 25, and 50 ng caused dose-dependent fevers in both PVN-lesioned and sham-operated animals, which at lower doses were smaller in the lesioned animals than in the sham-operated animals. Intraperitoneal lipopolysaccharide application, 50 micrograms/kg body wt, evoked a significantly lower febrile response in PVN-lesioned animals than in controls. The body temperature of PVN-lesioned animals and controls showed no difference during 300 min of exposure to heat (32 degrees C) or cold (7 degrees C). These results suggest that the PVN contributes to the complex regulation of temperature during the febrile response but not during the maintenance of normal body temperature.

Animals↗
PubMed1994

Rapid effect on suckling of an oxytocin antisense oligonucleotide administered into rat supraoptic nucleus.

Suckling in the lactating rat (days 6-10 of lactation) was used to characterize the effects of intracerebral oxytocin (Oxt) antisense oligonucleotide treatment on the hypothalamo-neurohypophysial system. Vehicle, mixed bases, Oxt antisense, or vasopressin antisense oligonucleotides (2.5 micrograms/0.5 microliter each) were infused directly into the left and right supraoptic nucleus (SON), 4 h before a litter of 10 pups was allowed to suckle for 30 min. In the Oxt antisense group, there was a significant reduction in the number of milk ejection reflexes (to 34.6 +/- 4.88%, P < 0.001), as well as in the weight gain of the litter (to 18.8 +/- 6.98%, P < 0.03) compared with vehicle (100%)-, mixed base-, or vasopressin antisense-treated animals, which did not differ from each other. The time to onset of suckling, however, was unchanged. Compared with presuckling values, plasma Oxt was significantly increased in all four groups 30 min after onset of suckling (vehicle, to 325 +/- 117%; mixed bases, to 258 +/- 48.2%; vasopressin antisense, to 330 +/- 55.7%), but this increase was less pronounced in Oxt antisense-treated rats (to 157 +/- 20.5%; P < 0.05 vs. vasopressin antisense). In contrast to these changes in neuroendocrine functions during suckling, Oxt as well as vasopressin content and Oxt immunoreactivity in posterior pituitaries and the SON, respectively, did not differ among groups. Our data indicate rapid and specific effects of an Oxt antisense oligonucleotide infused into the SON on neuroendocrine, suckling-related parameters that are not due to depleted stores of Oxt in the hypothalamo-neurohypophysial system.

Animals↗
PubMed1994

Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8.

Simultaneous microdialysis in brain and blood was used to monitor the effects of systemic and central cholecystokinin octapeptide (CCK-8) on the release of oxytocin and vasopressin within the hypothalamic supraoptic nucleus (SON) as well as into blood of urethan-anesthetized female rats. Administration of CCK-8 (20 micrograms/kg iv) increased oxytocin contents in 30-min microdialysates sampled simultaneously within the SON (1.8-fold) and blood (2.4-fold, both P < 0.05) compared with prestimulation levels. In another experiment, after bilateral administration of CCK-8 directly into the SON (10 ng/0.5 microliter) via a microdialysis/infusion probe, oxytocin contents in dialysates sampled from the left and right SON were increased 2.3- and 1.7-fold (P < 0.05), respectively. In simultaneously sampled dialysates from the jugular vein, oxytocin content increased 2.3-fold (P < 0.05). In contrast, oxytocin in dialysates sampled outside the hypothalamic nuclei was not altered by systemic or central CCK-8. The direct infusion of CCK-8 into both SON increased the release of vasopressin within the SON 1.7-fold (P < 0.05) but failed to significantly change vasopressin release into blood. The present findings show a coordinated regulation of intranuclear and systemic release of oxytocin in response to systemic and central CCK-8 and provide further evidence for a possible involvement of endogenous oxytocin in the complex regulation of ingestive and reproductive behaviors induced by CCK-8 at the brain level.

Animals↗
PubMed1993

Interleukin-1 beta has excitatory effects on neurons of the bed nucleus of the stria terminalis.

Arginine vasopressin (AVP) is an endogenous antipyretic which acts in the ventral septal area (VSA) of the brain following its release from terminals of neurons from the bed nucleus of the stria terminalis (BST). The neurochemical mechanisms involved in the activation of these BST neurons are unknown. The present study was conducted to determine whether a naturally occurring brain cytokine (interleukin-1 beta, IL-1) selectively activates the population of BST neurons projecting to the VSA or another locus known to receive vasopressinergic input from the BST, the habenular nuclei (HAB). Single unit extracellular recordings were made from identified BST neurons in urethane-anesthetized rats. Human recombinant IL-1 applied iontophoretically or by micropressure, evoked marked excitations of long duration in 24% of all BST cells observed (n = 102 cells). Iontophoresis of sodium salicylate attenuated or reversed the effects of the cytokine in all cases tested. The selective and long-lasting excitatory actions of IL-1 on BST neurons are consistent with a direct CNS function for this cytokine. In addition, these results are compatible with a role for IL-1 in evoking AVP release from BST neurons during fever.

Animals↗
PubMed1993

Blockade by funnel web toxin of a calcium current in the intermediate pituitary of the rat.

The pharmacological sensitivities of the low threshold (LT) and high threshold (HT) calcium currents were studied using single electrode voltage clamp techniques in melanotrophs of the intact rat intermediate pituitary. The T-type LT current was selectively abolished by 200 microM nickel whereas the HT current was preferentially abolished by 25 microM cadmium. The HT current consisted of both sustained and inactivating components. The sustained portion of the HT current was increased by BAY K-8644 indicating the presence of an L-type current. The inactivating component of the HT current was not affected by omega-conotoxin, which blocks the N-type calcium current in many other cell types, but was rapidly and reversibly reduced by funnel-web toxin, a blocker of the P-type calcium channel. These data suggest the presence of a P-type channel in a neuroendocrine cell.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Arginine vasopressin-induced sensitization in brain: facilitated inositol phosphate production without changes in receptor number.

Arginine vasopressin (AVP) has been shown to have a unique sensitization effect whereby repeated injection of AVP into a lateral cerebral ventricle or a mediobasal region of the rat forebrain below the lateral septum and including the anterior hypothalamus referred to as the ventral septal area, causes enhanced motor responses to the ligand. To elucidate possible neuronal mechanisms responsible for AVP sensitization, 1) we determined the dose and the time required for the development and expression of AVP sensitization, and 2) we tested the hypotheses that AVP sensitization may result in a) alteration of septal AVP V1 receptor affinity or number, and/or b) alteration of septal AVP V1 receptor signal transduction (phosphatidylinositol hydrolysis) mechanisms. Our behavioral data show that the magnitude of AVP sensitization varies with dose and time, and the effect is dependent on the time interval between injections, in that an initial intracerebroventricular AVP injection enhances the sensitivity of the animals to the motor effects of similar AVP injections given 6 h to 6 days later but not to injections given hourly or weekly. No changes in septal AVP binding site density and affinity, as measured by [3H]AVP binding to septal synaptic plasma membrane, were found in sensitized animals; [3H]inositol monophosphate stimulation in response to AVP in septal slices, however, was found to be significantly enhanced. This enhanced [3H]inositol monophosphate stimulation appears specific to a V1-type receptor because it was significantly reduced in the presence of the V1 receptor antagonist, d(CH2)5Tyr(Me)AVP, and was not found using oxytocin or the V2 receptor agonist, DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Oxytocin pretreatment enhances arginine vasopressin-induced motor disturbances and arginine vasopressin-induced phosphoinositol hydrolysis in rat septum: a cross-sensitization phenomenon.

The recent observation that the central oxytocin (OT) receptor has high affinity for both OT and arginine vasopressin (AVP) raises the possibility that it may be involved in some of the central actions of AVP. Repeated intracerebroventricular (icv) injections of AVP in rats evoke an unusual sensitization phenomenon in that a first exposure to the peptide enhances the sensitivity (sensitization) of the brain to a second exposure. This report investigates the possibility that the OT receptor may be involved in the mediation of the phenomenon of sensitization, using OT, a specific OT receptor agonist, [Thr4,Gly7]OT, and a specific OT receptor antagonist, d(CH2)5,[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (compound 6; cpd 6), as well as a V1 AVP receptor antagonist, d(CH2)5Tyr(Me)AVP. Peptides were injected icv in conscious, adult male Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cortical spreading depression blocks prostaglandin E1 and endotoxin fever in rats.

We have tested the hypothesis that the cortex may play a role in the development of fever. Male Sprague-Dawley rats equipped with AM transmitters for telemetric measurement of body temperature were given intracerebroventricular prostaglandin E1 (PGE1), corticotropin-releasing hormone (CRH), or intravenous E. coli endotoxin. Application of cotton pellets soaked with 3.3 M KCl to the frontal cortex (to induce spreading depression) significantly reduced fevers to PGE1 and endotoxin when compared with fever magnitude with 0.9% NaCl application to the cortex. Neither CRH-induced hyperthermia nor normal body temperatures were altered by the spreading depression. Our results reveal a novel action of spreading depression on thermoregulatory function and indicate cortical involvement in the development of fever.

Alprostadil↗
PubMed1993

Possible involvement of brain oxytocin in modulating vasopressin antipyretic action.

Experiments were undertaken to test whether oxytocin (OT) may modulate the antipyretic action of arginine vasopressin (AVP) and to determine whether the action of endogenously released OT and/or AVP evoked by fever may modulate the motor actions of exogenous AVP. Intracerebroventricular (icv) injection of interleukin-1 alpha (IL-1 alpha, 40 ng) elicited a significantly attenuated rise in body temperature during the 2nd h of the febrile responses in OT-pretreated (0.1-10 pmol icv, 24 h earlier) rats. At the end of the 2nd h, administration of AVP (1 pmol icv), but not OT (10 pmol icv), significantly suppressed the febrile response in OT-pretreated but not in saline-pretreated rats. In nonfebrile OT-pretreated rats, 10 but not 1 pmol of AVP (icv) caused a significant decrease in body temperature. In rats pretreated with IL-1 alpha (40 ng icv) injection of AVP (100 pmol icv) induced enhanced motor responses. In summary, the ability of OT pretreatment to alter the febrile response to IL-1 alpha and the antipyretic action of AVP suggests a role for this peptide in fever. Furthermore, the observation that fever pretreatment can lower the threshold for convulsive-like behavior evoked by subsequent exposure to AVP raises the possibility that central OT and/or AVP released during fever could play a role in the genesis of febrile convulsions.

Animals↗
PubMed1993

Simultaneous microdialysis in blood and brain: oxytocin and vasopressin release in response to central and peripheral osmotic stimulation and suckling in the rat.

Simultaneous microdialysis in blood and brain has been used to monitor the release of both oxytocin and vasopressin into the systemic circulation (jugular vein/right atrium) and within the hypothalamic supraoptic nucleus of rats. Both home-made probes for blood and brain microdialysis revealed detectable nonapeptide concentrations under basal conditions and differential responses to a variety of stimuli. In urethane-anesthetized male rats, bilateral stimulation of the supraoptic nucleus by microdialyzing hypertonic medium (1 M NaCl) not only significantly increased the intranuclear release of both oxytocin and vasopressin (p < 0.05), but also their release from the neurohypophysis into blood (p < 0.05). In poststimulation microdialysates sampled from blood, the nonapeptides reached basal levels again, whereas intranuclear levels were further elevated. Intraperitoneal injection of hypertonic saline, on the other hand, resulted not only in the well-known increased peripheral release of oxytocin and vasopressin (p < 0.01 each), but also in a delayed increase in intranuclear oxytocin (p < 0.05). In contrast, intranuclear vasopressin release failed to change within the 90-min period following osmotic stimulation. In conscious lactating rats, suckling increased oxytocin contents in microdialysates sampled simultaneously in blood and the supraoptic nucleus (p < 0.05 each) further validating the microdialysis techniques used. The in vivo recovery in blood of approximately 65% determined using both radiolabeled and endogenous oxytocin provides a rough estimate to assess nonapeptide concentrations in plasma from 30-min or even 10-min blood microdialysis data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Postsynaptic potentials mediated by GABA and dopamine evoked in stellate glial cells of the pituitary pars intermedia.

Studies have shown that many glial cells in the CNS possess receptors for neurotransmitters and that synapse-like contacts exist between glial cells and axonal terminals. Although synapse-like contacts are present between the glial cells (stellate cells) of the pituitary pars intermedia and the axons from the arcuate nucleus, it is not known whether these cells are under synaptic control. The objective of the present study was to determine whether transmitter-mediated postsynaptic potentials occurred in the stellate cells of the rat pituitary pars intermedia. Whole pituitaries were maintained in vitro, and a stimulating electrode was placed on the stalk to activate afferent fibers. Intracellular recordings were obtained with sharp microelectrodes. Stellate cells showed electrophysiological characteristics of macroglia including a resting potential more negative than -65 mV, low input resistance (< 50 M omega), and no detectable voltage-activated conductances. Single-pulse afferent nerve (stalk) stimulation evoked a [Ca2+]o-dependent postsynaptic response in the stellate cells consisting of a depolarization (< 500 msec) and a long-lasting hyperpolarization (45-75 sec). The depolarization was mimicked by GABA application and blocked by the GABAA antagonist bicuculline (100 microM). Repetitive stimulation of the stalk increased the amplitude and prolonged the GABA-mediated depolarization, during which a decrease in input resistance was observed. The hyperpolarization was mimicked by dopamine and blocked by the D2 antagonists sulpiride (2 microM) and domperidone (10 microM). Nipecotic acid (100 microM; an inhibitor of GABA uptake) or GBR 12909 (15 microM; an inhibitor of dopamine uptake) had minimal effects on the synaptic responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Vasopressin-induced motor effects: localization of a sensitive site in the amygdala.

Arginine vasopressin (AVP) induces motor effects when administered into the cerebral ventricles, the ventral septal area (VSA), or the vestibular cerebellum of the rat brain. Because AVP-like immunoreactivity and AVP-binding sites exist in the central medial amygdala (cmeA), and because the amygdala can be kindled to produce motor effects, we hypothesized that the amygdala might play a role in AVP-induced motor effects. This hypothesis was tested by observing motor behavior in response to injection of AVP into the central medial region of the amygdala. Our results demonstrate that an initial injection of AVP into the cmeA caused minor motor effects, including immobility, prostration and ataxia, whereas a similar injection, given 24 h later, caused severe motor effects including barrel rotations and myoclonic/myotonic-like convulsive behavior. A potential receptor basis for the AVP-induced motor and sensitization effects in the cmeA was investigated using AVP analogues. A V1 antagonist, d(CH2)5Tyr(Me)AVP, blocked both the motor and sensitization effects produced by cmeA AVP injection. A V2 receptor agonist, DDAVP, did not affect motor activity upon cmeA injection, but did, however, sensitize animals to subsequent cmeA AVP injection. These results suggest that the cmeA is a sensitive site for AVP-induced motor effects and that these motor effects are sensitized by prior exposure to AVP. While the motor effects observed after cmeA AVP injection are mediated via AVP receptors that resemble the V1 type, the sensitization effect may be mediated via multiple receptor systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1992

Vasopressin perfusion within the medial amygdaloid nucleus attenuates prostaglandin fever in the urethane-anaesthetized rat.

The antipyretic effect of arginine vasopressin (AVP) introduced into the ventral septal area (VSA) by push-pull perfusion was investigated in the urethane-anaesthetized rat. In addition, experiments were carried out to determine whether AVP could suppress fever when similarly perfused within the medial amygdaloid nucleus (meA). During push-pull perfusion of artificial cerebrospinal fluid within the VSA or meA, PGE1 injected intracerebroventricularly evoked fevers with respective magnitudes of 1.3 +/- 0.2 degrees C and 1.4 +/- 0.3 degrees C above baseline. Perfusion of AVP (6.5 micrograms/ml) within the VSA had significantly reduced the magnitude of PGE1 fever to 0.3 +/- 0.3 degrees C above baseline, while having no significant effect on afebrile colonic temperature. Perfusion of AVP (6.5 micrograms/ml) within the meA had significantly attenuated the magnitude of PGE1 fever to 0.7 +/- 0.2 degrees C above baseline, while having no significant effect on afebrile colonic temperature. These results support further the utility of the urethane-anaesthetized rat model for future investigations of the central control of fever and antipyresis. In addition, these data are consistent with the hypothesis that AVP may act within the meA as an endogenous antipyretic.

Alprostadil↗