Push-pull perfusion and microdialysis studies of central oxytocin and vasopressin release in freely moving rats during pregnancy, parturition, and lactation.
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Animals↗
Biomedical subjects
Q J Pittman
Publications and source records attributed to Q J Pittman.
Vasopressin involvement in central control of blood pressure.
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Animals↗
Central arginine vasopressin and endogenous antipyresis.
Arginine vasopressin (AVP) is a centrally synthesized nonapeptide that exerts classical endocrine effects as well as a host of centrally mediated actions. A strong case can be argued in support of a neurotransmitter-neuromodulator role for AVP. Acting within the central nervous system (CNS), AVP has been demonstrated to be involved in the modulation of febrile body temperature. Because AVP acts to reduce pyrogen-induced fevers, but not normal body temperature, its actions are deemed to be antipyretic. However, to demonstrate an endogenous antipyretic function, AVP must be shown to be active during conditions where fever is naturally suppressed. This review will focus on five such conditions where the absence of pyrogen-induced fever can be linked to the endogenous activity of AVP within the brain. In the neonatal rat pup, the use of specific antagonists to the AVP receptor has revealed a role for CNS AVP in the absence of fever following peripheral injections of bacterial endotoxin. These results may help to explain a similar lack of fever in other newborn species. In parturient animals a reduced or absent febrile response has been linked to the increased presence of AVP within the septal area of the brain. The combined use of AVP receptor antagonism as well as immunohistochemistry has shown enhanced AVP activity within the ventral septal area of the rat and guinea pig brain during tolerance to intravenous pyrogens. These results suggest that the mechanism of fever suppression following repeated systemic injections of bacterial pyrogen includes centrally acting AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Vasopressin-induced antipyresis in the medial amygdaloid nucleus of conscious rats.
Experiments were undertaken to characterize a possible receptor mediating antipyretic action of arginine vasopressin (AVP) within the medial amygdaloid nucleus (meA) in the conscious rat. Additional experiments were directed at determining whether the action of endogenously released AVP can be revealed in the meA during fever in the conscious rat. These objectives were achieved using vasopressin analogues directed against vasopressor (V1a) and antidiuretic (V2) receptors. Bilateral injection of AVP (40 pmol) into the meA of conscious rats suppressed fever evoked by intracerebroventricular (icv) administration of prostaglandin E1 (PGE1, 50 ng). The V2 receptor agonist 1-desamino-8-D-AVP (40 pmol) injected into the meA evoked only moderate antipyresis compared with AVP, possibly because of interaction of this agonist with V1a receptors. The antipyretic effect of AVP was blocked when injection of the peptide was preceded by a bilateral injection of the V1a antagonist 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine AVP [d(CH2)5Tyr(Me)AVP, 400 pmol] into the meA. Injection of d(CH2)5Tyr(Me)AVP alone into the meA was without significant effect on afebrile core temperature. Injection of d(CH2)5Tyr(Me)AVP or 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-D-valine,4-valine AVP (a V2 antagonist) alone into the meA before icv PGE1 resulted in fevers that were not significantly different from artificial cerebrospinal fluid controls. These data are consistent with the possibility that AVP might act within the meA to evoke antipyresis via receptors that resemble V1a (vasopressor) receptors. However, the action of AVP endogenously released into the meA does not appear to be an absolute requisite in the normal modulation of PGE1 fever.
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Ca(2+)- and voltage-dependent inactivation of Ca2+ currents in rat intermediate pituitary.
We used single electrode voltage-clamp methods to investigate the inactivation of Ca2+ currents in melanotrophs of the intermediate lobe of the pituitary. The low threshold transient current was inactivated by brief prepulses to potentials above -30 mV and inhibition remained complete as prepulse potential was increased from 0 to +70 mV. Both the high threshold transient and sustained currents, however, were inhibited to the greatest extent (60%) by prepulses to 0 mV. Prepulses to more positive potentials close to the Ca2+ reversal potential produced much less (15%) inactivation. Buffering intracellular Ca2+ by including BAPTA in the recording electrode or replacing extracellular Ca2+ with Ba2+ reduced the effect of prepulses. Slowing Ca2+ extrusion by reducing the Na+ gradient across the cell increased the duration of the effect of prepulses. We conclude that the low threshold, transient current is inactivated primarily by membrane voltage while both the high threshold currents are inhibited by elevation of intracellular Ca2+ although the two currents display different sensitivities to Ca2+ concentration. Inhibition of the high threshold transient current by the neurotransmitter dopamine, however, acts by a different mechanism not mediated by Ca(2+)-dependent inactivation.
Animals↗
Septal and hippocampal release of vasopressin and oxytocin during late pregnancy and parturition in the rat.
The push-pull perfusion technique, in conjunction with specific radioimmunoassays, was used to monitor the release of both arginine vasopressin (AVP) and oxytocin (OXT) within distinct limbic brain areas of conscious female rats. In pregnant rats near term, the release of AVP was greater than that of virgin rats in both the ventral (p less than 0.001) and mediolateral (p less than 0.001) septal areas; similarly, release of OXT increased in the ventral septal area (p less than 0.01) at this time. In contrast, no changes in the levels of either peptide occurred in the dorsal hippocampus. In parturient rats, AVP release tended to decrease in the septal areas but increased fivefold in the dorsal hippocampus (p less than 0.001) compared to pregnant animals. In contrast, OXT levels assayed in the same perfusates did not differ from those observed in pregnant animals. Plasma levels of AVP in pregnant rats (p less than 0.05) and of OXT in parturient animals (p less than 0.01) were found to be increased over levels in virgin rats. The regionally different and peptide-specific changes in release pattern of AVP and OXT in virgin, pregnant and parturient rats may be of physiological significance in antipyresis and behaviors accompanying parturition.
Animals↗
Arginine vasopressin induced motor disturbances in the medial amygdala: evidence for the involvement of a V1-type of AVP receptor.
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Amygdala↗
Septal arginine vasopressin (AVP) receptor regulation in rats depleted of septal AVP following long-term castration.
Arginine vasopressin (AVP) causes severe motor disturbances, including barrel rotations and myotonic/myoclonic convulsions, following repeated injections into either a lateral cerebral ventricle or the ventral septal area (VSA) of the rat brain. Because the AVP content of the rat septal area has been shown to be virtually eliminated following long-term castration, and because removal of a receptor ligand typically results in receptor upregulation and behavioral supersensitivity to the ligand, we tested the hypothesis that long-term castrated rats may be supersensitive to the motor actions caused by centrally injected AVP and may have upregulated septal AVP receptors. In these experiments, adult male Wistar rats were used 5 months after castration or, as controls, after sham castration. The effectiveness of long-term castration in eliminating AVP content of the VSA was indicated by the observation that a priming hypertonic saline stimulus (known to induce the central release of AVP and sensitize the rat brain) sensitized the brains of sham control rats but not of the castrated rats to the motor actions of a subsequent intracerbroventricular injection of AVP. The motor actions of centrally injected AVP, as well as septal AVP receptor characteristics (number and affinity), and AVP-stimulated phosphoinositide (PI) hydrolysis were then investigated in long-term castrated and sham control rats. Motor disturbances induced by either a first or a second injection of AVP were not greater in long-term castrated rats than in sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Depletion of brain alpha-MSH alters prostaglandin and interleukin fever in rats.
Alpha-melanocyte stimulating hormone (alpha-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P less than 0.05) than those of the controls for the lower dose of PGE1 at 10-30 min and for IL-1 at 3-6 h after the injections. MSG-treated rats showed significant reduction (P less than 0.01) in alpha-MSH content of the medial basal hypothalamus and lateral septum when compared to saline controls. Body temperature response of non-febrile animals to high ambient temperature was not affected by the MSG treatment. These data support the hypothesis that alpha-MSH is an endogenous antipyretic in the rat.
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Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin.
Experiments were conducted (i) to determine the hemodynamic (blood pressure and heart rate) responses of conscious rats following intrathecal (IT) administration of endogenous prodynorphin-derived opioids into the lower thoracic space, (ii) to identify the receptors involved in mediating their cardiovascular responses, and (iii) to reveal any possible hemodynamic interactions with the neuropeptide arginine vasopressin. Male Sprague-Dawley rats were surgically prepared with femoral arterial and venous catheters as well as a spinal catheter (into lower thoracic region, T9-T12). After recovery, hemodynamic responses were observed in conscious rats for 5-10 min after IT injections of artificial cerebrospinal fluid (CSF) solution, prodynorphin-derived opioids (dynorphin A, dynorphin B, dynorphin A (1-13), dynorphin A (1-10), alpha- and beta-neoendorphin, leucine enkephalin (LE), methionine enkephalin (ME), arginine vasopressin (AVP), or norepinephrine (NE)). IT injections of AVP (10 or 20 pmol), dynorphin A (1-13), or dynorphin A (10-20 nmol) caused pressor effects associated with a prolonged and significant bradycardia. Equimolar (20 nmol) concentrations of LE, ME, alpha- and beta-neoendorphin, and dynorphin A (1-10) caused no significant blood pressure or heart rate changes. Combined IT injections of dynorphin A (1-13) and AVP caused apparent additive pressor effects when compared with the same dose of either peptide given alone. IT infusion of the specific AVP-V1 antagonist d(CH2)5Tyr(Me)AVP before subsequent IT AVP, dynorphin A (1-13), or NE administration inhibited only the subsequent pressor responses to AVP. The kappa-opioid antagonist (Mr2266) infused IT blocked the pressor actions of subsequent dynorphin A administration and not AVP or NE.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Release of vasopressin and oxytocin by paraventricular stimulation in rats.
The nucleus tractus solitarius/dorsal motor nucleus of the vagus nerve (NTS/DMV) area was perfused by the push-pull perfusion technique in anesthetized rats, and perfusates were assayed for arginine vasopressin (AVP) and oxytocin (OXT) immunoreactivity. As compared with controls, electrical stimulation of the ipsilateral paraventricular nucleus (PVN) resulted in increased amounts of both AVP (approximately 5-fold) and OXT (approximately 10-fold, P less than 0.05 each) in the perfusates. During the poststimulation perfusion period, peptide concentrations were found to return to control levels. Elevation of circulating AVP and OXT by an osmotic stimulus did not result in increases of AVP and OXT in NTS/DMV perfusates. These data suggest that AVP and OXT are released from NTS/DMV area fiber terminals during electrical stimulation of descending PVN neurons. Furthermore, they are consistent with the view that both peptides are involved as neurotransmitters in autonomic regulation.
Animals↗
Vasopressin and oxytocin in rat brain in response to prostaglandin fever.
Urethan-anesthetized rats were used to identify effective stimuli for the release of the peptides arginine vasopressin (AVP) and oxytocin into the ventral septal area (VSA) of the brain. Febrile responses to intracerebroventricular injection of prostaglandin E1 (PGE1) were observed in rats whose body temperatures were maintained at 35, 37, or 39 degrees C. Microinjection of the AVP antagonist d(CH2)5Tyr(Me)AVP into the VSA enhanced fever only when PGE1 administration was associated with a significant rise in body temperature. Passive elevation ("artificial fever") or reduction of body temperature in the absence of a PGE1 stimulus was not affected by the antagonist. Push-pull perfusion of the VSA and the dorsal hippocampus, followed by radioimmunoassay of perfusates for AVP and oxytocin, revealed enhanced release into the VSA of AVP only when PGE1 administration was followed by a rise in body temperature. Oxytocin was released whenever body temperature was raised. Peptide concentrations in simultaneous perfusates of dorsal hippocampus did not change in response to PGE1 administration or to passive elevation of body temperature. We conclude that AVP is released into the VSA, but not the dorsal hippocampus, of the rat during a fever induced by PGE1. Oxytocin is released into the VSA, but not the hippocampus, when temperature is elevated.
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Synaptic modulation by dopamine of calcium currents in rat pars intermedia.
Melanotrophs of the rat pars intermedia are innervated by dopaminergic fibers traveling through the pituitary stalk which inhibit secretion via an action on D-2 receptors. As secretion from the melanotroph has been shown to be calcium (Ca2+) dependent, it is possible that dopamine may have an action to inhibit Ca2+ currents in these cells. This possibility was tested by examining the effects of exogenously applied dopaminergic agonists or synaptically released dopamine upon Ca2+ currents recorded under single electrode voltage clamp in intact rat pars intermedia in vitro. Following blockade of sodium and potassium currents in melanotrophs, Ca2+ spikes were elicited with intracellular injection of depolarizing currents; electrical stimulation of the pituitary stalk caused an inhibition of the Ca2(+)-based action potentials which lasted for several seconds. Using single-electrode voltage-clamp techniques, we recorded inward Ca2+ currents corresponding to the T, N, and L types (see Williams et al., 1990). Stimulation of the pituitary stalk inhibited both the low- and high-threshold peak inward Ca2+ currents elicited from a holding potential of -90 mV. In contrast, when noninactivating Ca2+ currents were elicited from a holding potential of -30 mV, the currents were not altered by stalk stimulation. This pattern of inhibition of the Ca2+ currents was consistent with the preferential inhibition, by stalk stimulation, of the N and T Ca2+ currents, while sparing the L current. We observed that inhibition of Ca2+ currents due to stalk stimulation was completely reversed by bath perfusion of domperidone (1 microM), an antagonist of dopamine at the D-2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Electrophysiological properties of neuroendocrine cells of the intact rat pars intermedia: multiple calcium currents.
Intracellular recordings for current and voltage clamping were obtained from 130 neuroendocrine cells of the pars intermedia (PI) in intact pituitaries maintained in vitro. Spontaneous and evoked action potentials were blocked by TTX or by intracellular injection of a local anesthetic, QX-222. After potassium (K+) currents were blocked by tetraethylammonium (TEA), 4-aminopyridine, and intracellular cesium (Cs+), 2 distinct calcium (Ca2+) spikes were observed which were differentiated by characteristic thresholds, durations, and amplitudes. Both Ca2+ spikes were blocked by cobalt (Co2+) but were unaffected by TTX or QX-222. The low-threshold spike (LTS) had a smaller amplitude and inactivated when membrane potential was depolarized past -40 mV or when evoked at a fast rate (greater than 0.5 Hz). The high-threshold spike (HTS) typically had a larger amplitude and longer duration, was not inactivated at potentials which inactivated the LTS, and could be evoked at rates of up to 10 Hz. Single-electrode voltage-clamp analysis revealed that 3 distinct components of the Ca2+ current were present in most cells. From a negative holding potential (-90 mV), 2 separate peak inward currents were observed; a low-threshold transient current, similar to a T-type Ca2+ current, activated at -40 mV, whereas a large-amplitude inactivating current activated above -20 mV. This large inactivating Ca2+ current was significantly inactivated at a holding potential of -40 mV or by brief prepulses to positive potentials, and was similar to an N-type Ca2+ current. A sustained Ca2+ current (L-type) was observed which was not altered by different holding potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Presynaptic inhibition by neuropeptide Y and baclofen in hippocampus: insensitivity to pertussis toxin treatment.
Neuropeptide Y (NPY) presynaptically inhibits excitatory transmission in area CA1 of rat hippocampus. As postsynaptic NPY receptors in certain other tissues have been shown to be coupled to G-proteins, we have tested the hypothesis that the hippocampal NPY effects are also mediated by G-proteins. Pretreatment of rats with pertussis toxin (PTX) was ineffective in blocking NPY's presynaptic inhibitory actions in area CA1 of the hippocampal slice. The presynaptic inhibitory action of baclofen was also unaffected by PTX pretreatment. However, in these same PTX-pretreated slices, the postsynaptic hyperpolarizing actions of baclofen and 5-hydroxytryptamine were blocked. We suggest that pre- and postsynaptic receptors possess different coupling mechanisms to their effectors.
Animals↗
Single-unit activity in the bed nucleus of the stria terminalis during fever.
Arginine vasopressin, released from nerve terminals in the septal region, probably exerts endogenous antipyretic activity. A major source of vasopressin to this area is the bed nucleus of the stria terminalis (BST). In order to characterize electrophysiologically the BST-septal pathway and its potential role in the control of fever, single-unit, extracellular recordings were made from neurons in the BST of anesthetized rats. Afferent and efferent connections were identified by electrical stimulation of the medial amygdaloid nucleus and the ventral septal area (VSA). BST neurons received both inhibitory and excitatory synaptic input from the amygdala and VSA. Efferents to the VSA were identified by stimulus-evoked antidromic spike invasion. Some BST neurons were responsive to peripheral skin temperature (thermoresponsive). The activity of putative vasopressin neurons was studied during prostaglandin E1-induced fever. Although a majority of BST units was unaffected by fever, a proportion of the cells examined increased their firing rates in accordance with reported release of vasopressin in the VSA during fever.
Action Potentials↗
Identification of a GABA-activated chloride-mediated synaptic potential in rat pars intermedia.
Intracellular recordings from melanotrophs in acutely isolated, intact pituitaries revealed inhibitory postsynaptic potentials (IPSPs) resulting from both pituitary stalk stimulation and exogenous gamma-aminobutyric acid (GABA) application. The stalk-stimulated and GABA-evoked IPSPs displayed identical conductance increases to chloride ions. Both responses reversed in polarity at the same membrane potential and were blocked with bicuculline, a GABAA antagonist. We conclude that activation of this synapse releases GABA which acts on a classical GABAA receptor to increase conductance to chloride in the melanotroph.
Action Potentials↗
A dopaminergic inhibitory postsynaptic potential mediated by an increased potassium conductance.
Intracellular recordings from intact pituitary melanotrophs show that, in the same cell, inhibitory postsynaptic potentials resulting from either pituitary stalk stimulation or exogenous dopamine are abolished by D2 receptor antagonists, display identical conductance changes, are reversed in polarity at the same membrane potential and are sensitive to pertussis toxin pretreatment. The reversal potential of the inhibitory postsynaptic potential shows a 65 mV shift with a 10-fold change in external potassium concentration, which is close to that predicted by the Nernst equation. We conclude that activation of this synapse releases dopamine which acts on a D2 receptor to increase potassium conductance via a G-protein-mediated mechanism. This is the first characterization of an inhibitory dopaminergic synapse in the mammalian nervous system.
Action Potentials↗