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P Poulin

Publications and source records attributed to P Poulin.

47 records · Page 3Linked to original sources
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↗
PubMed1991

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↗
PubMed1988

[3H]arginine vasopressin binding to rat brain: a homogenate and autoradiographic study.

Arginine-vasopressin (AVP) has been implicated as a putative central neurotransmitter or neuromodulator in some brain functions. This study demonstrates binding of [3H]AVP to rat brain homogenates that is pH and temperature dependent, is saturable (Kd = 0.77 nM, Bmax = 0.374 pmol/mg) and reversible. A number of AVP analogues competitively displaced the [3H]AVP binding, indicating that central AVP binding sites may have a resemblance to the peripheral (V1) AVP vasopressor receptor. Homogenate binding occurred predominantly in the microsomal fraction (P3) of the hypothalamus while in the hippocampus and septum binding was predominantly in the synaptosomal fraction (P2). Autoradiographic methods showed displaceable [3H]AVP binding in the lateral septum, amygdala, supraoptic, paraventricular and suprachiasmatic nuclei of the hypothalamus supporting the results of homogenate binding in preparations of these regions.

Animals↗
PubMed1988

The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders.

Perfusion of the peptide, arginine vasopressin (AVP), within the ventral septal area (VSA) of the brain of a number of species reduces fever but not normal body temperature. This antipyretic response appears to be mediated by AVP receptors of the V1 subtype. Lesions of the VSA with kainic acid are associated with prolonged and enhanced fevers in rats. A role for endogenous AVP in fever suppression within the VSA comes from several types of experiments: (1) AVP release within the VSA is inversely correlated to fever height; (2) AVP antagonists or antiserum injected into the VSA prolong fever; (3) animals lacking endogenous AVP in the VSA (Brattleboro rat, long-term castrated rat) develop enhanced fevers. Electrical stimulation of the AVP-containing cell bodies of the bed nucleus of the stria terminalis (BST) orthodromically inhibits VSA neurons and also suppresses fever; the latter effect can be abolished with application of a V1 antagonist to the VSA. Iontophoretic studies indicate that AVP inhibits glutamate-stimulated activity of thermoresponsive and other VSA neurons. AVP can also act in the VSA to cause severe motor disturbances; this action is receptor mediated and increases in severity upon sequential exposure to AVP. Because sites of action of the antipyretic and convulsive action of AVP are similar, and because animals lacking brain AVP display reduced convulsive activity, it is possible that AVP, released during fever, could be involved in the genesis of convulsive activity.

Action Potentials↗
PubMed1988

Subcellular localization and characterization of vasopressin binding sites in the ventral septal area, lateral septum, and hippocampus of the rat brain.

[Arg8]-Vasopressin (AVP) has been shown to exert characteristic central physiological actions in the ventral septal area of the rat brain. This study reports the characterization of receptors for AVP in synaptic plasma membranes prepared from the ventral septal area, the lateral septum, and the hippocampus. Binding of [3H]AVP was temperature and time dependent, linearly related to protein concentration, saturable, and specific. Scatchard plot analysis suggested the presence of a population of binding sites in the three brain areas with dissociation constants and maximal binding capacities, respectively, of 1.06 +/- 0.39 nM and 24.0 +/- 7.01 fmol/mg of protein (mean +/- SEM; n = 3 for the ventral septal area, 0.92 +/- 0.13 nM and 47.0 +/- 4.96 fmol/mg of protein (n = 3) for the lateral septum, and 0.91 +/- 0.14 nM and 25 +/- 5.02 fmol/mg of protein (n = 3) for the hippocampus. In all three brain regions, the rank order of potencies of several vasopressin analogs, unrelated peptides, and other compounds for competitive displacement of ligand indicated a receptor with properties resembling those of the V1-like receptor for AVP. These data document the presence of a high-affinity, V1-like vasopressin receptor in the rat ventral septal area for which the pharmacological properties are similar to those previously reported in physiological studies.

Animals↗
PubMed1986

Autoradiographic localization of binding sites for vasoactive intestinal peptide (VIP) in bovine cerebral arteries.

A substantial body of published evidence indicates that vasoactive intestinal peptide (VIP) may function as a vasodilatory neurotransmitter to cerebral blood vessels via a specific VIP receptor. In the present study in vitro autoradiography utilizing monoiodinated [125I-Tyr10]-VIP demonstrated VIP binding sites in the medial layer of bovine anterior, middle, and posterior cerebral arteries. This observation is consistent with the VIP receptor being localized in vascular smooth muscle components.

Animals↗
PubMed1986

Radioimmunoassays for fish tail neuropeptides: II. Development of a specific and sensitive assay for and the occurrence of immunoreactive urotensin II in the central nervous system and blood of Catostomus commersoni.

A sensitive radioimmunoassay (RIA) based on an antiserum to synthetic Gillichthys mirabilis urotensin II (UII) generated in rabbits, reacting with all known forms of the UII peptides, was developed. The UII was iodinated by either the chloramine-T or the lodogen method and was purified by high-pressure liquid chromatography. The antiserum, at a final dilution of 1:125,000, gave 50% binding of the iodinated UII. The sensitivity of the RIA was 1.8 +/- 0.2 pg/assay tube (1.2 +/- 0.2 fmol/tube; n = 7). Crossreactivity studies with various UII peptides, modified UII peptides, and fragments indicated that the immunoreactive recognition site of this antiserum is directed to the disulfide ring region (positions 6-11) of the UII peptides. Somatostatin 14, which has the part sequence 7-9 in common with UII peptides, did not crossreact. No detectable crossreactivity with urotensin I, urophysin B or D from Catostomus commersoni, arginine vasopressin, or arginine vasotocin could be shown. Displacement curves obtained with standard extracts of G. mirabilus urophyses were similar to those of synthetic G. mirabilus UII. comparison of RIA and bioassay of G. mirabilis urophysial extracts showed good correlation. Immunoreactive UII was detected in different parts of the brain, spinal cord, and blood of C. commersoni.

Animals↗
PubMedDate not supplied

An approach for incorporating tissue composition data into physiologically based pharmacokinetic models.

The objective of this study was to develop an approach for incorporating tissue composition data into physiologically based pharmacokinetic (PBPK) models in order to facilitate "built-in" calculation of tissue: air partition coefficients (PCs) of volatile organic chemicals. The approach involved characterizing tissue compartments within PBPK models as a mixture of neutral lipids, phospholipids, and water (instead of using the conventional description of them as "empty" boxes). This approach enabled automated calculation of the tissue solubility of chemicals from n-octanol and water solubility data, since these data approximate those of solubility in tissue lipids and water. Tissue solubility was divided by the saturable vapor concentration at 37 degrees C to estimate the tissue: air PCs within PBPK models, according to the method of Poulin and Krishnan (1995c). The highest and lowest lipid and water levels for human muscle, liver, and adipose tissues were obtained from the literature and incorporated within the tissue composition-based PBPK model to calculate the tissue: air PCs of dichloromethane (DCM) and simulate the pharmacokinetics of DCM in humans. The PC values predicted for human tissues were comparable to those estimated using rat tissues in cases where the relative levels of lipids and water were comparable in both species. These results suggest that the default assumption of using rat tissue: air PCs in human PBPK models may be acceptable for certain tissues (liver, adipose tissues), but questionable for others (e.g., muscle). The PBPK modeling exercise indicated that the interindividual differences in tissue dose arising from variations of tissue: air PCs may not be reflected sufficiently by venous blood concentrations. Overall, the present approach of incorporating tissue composition data into PBPK models would not only enhance the biological basis of these models but also provide a means of evaluating the impact of interindividual and interspecies differences in tissue composition on the tissue dose surrogates used in PBPK-based risk assessments.

Adipose Tissue↗