Biomedical subjects

J W Gunnet

Publications and source records attributed to J W Gunnet.

5 recordsLinked to original sources

PubMed1991

3-Methoxy-4-hydroxyphenylethyleneglycol concentrations in discrete hypothalamic nuclei reflect the activity of noradrenergic neurons.

An analytical technique is described which permits the quantitation of picogram concentrations of 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG) in acid hydrolyzed extracts of microdissected regions of the rat brain, and this procedure is used to determine if alterations in the activity of noradrenergic neurons are reflected by changes in the concentrations of MHPG in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the rat hypothalamus. MHPG was not detected in non-hydrolyzed samples of either the PVN or SON, but following acid hydrolysis (heating of samples at 94 degrees C for 5 min in 0.16 M perchloric acid) MHPG was detected in both of these regions. These results indicate that MHPG exists primarily as a conjugate in the PVN and SON. Neurotoxin-induced lesions of the ventral noradrenergic bundle decreased norepinephrine (NE) and MHPG concentrations in the PVN and SON, demonstrating that tissue levels of MHPG in these brain regions are dependent upon the presence of noradrenergic neurons. Electrical stimulation of the locus coeruleus increased MHPG concentrations in the PVN, but not in the SON, whereas electrical stimulation of the medial forebrain bundle increased MHPG concentrations in both of these regions. The alpha 2-adrenergic receptor antagonist idazoxan increased, while the alpha 2-adrenergic receptor agonist clonidine decreased MHPG concentrations in both the PVN and SON, but neither idazoxan nor clonidine altered NE concentrations in these regions. Immobilization of rats in the supine position increased MHPG concentrations in the PVN and SON, and this was accompanied by a decrease in NE concentrations in the SON.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1991

Stress-induced secretion of alpha-melanocyte-stimulating hormone is accompanied by a decrease in the activity of tuberohypophysial dopaminergic neurons.

The purpose of the present study was to examine the acute effects of stress on the secretion of alpha-melanocyte-stimulating hormone (alpha MSH) and the activity of tuberohypophysial dopamine (DA) neurons in female and male rats. The activity of tuberohypophysial DA neurons was estimated by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) following administration of the decarboxylase inhibitor NSD 1015, and the concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the intermediate and neural lobes of the posterior pituitary. The combination of brief (2 min) ether exposure followed by 30 min of supine restraint (immobilization in the supine position) decreased the rate of DOPA accumulation in the intermediate, but not in the neural lobe of both female and male rats. Similarly, brief ether exposure followed by 10, 20 or 30 min of supine restraint increased plasma alpha MSH concentrations and decreased DOPAC concentrations in the intermediate lobe of female and male rats. In the absence of ether, tube restraint (confinement in a cylindrical acrylic tube) increased alpha MSH secretion and decreased intermediate lobe DOPAC concentrations, whereas ether in the absence of physical restraint had no effect. These results suggest that the stress-induced activation of alpha MSH secretion in both female and male rats may be due, in part, to a decrease in the activity of tuberohypophysial DA neurons in the intermediate lobe of the posterior pituitary.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effects of a sustained release formulation of the gonadotrophin-releasing hormone agonist histrelin on serum concentrations of gonadotrophins and oestradiol, and ovarian LH/human chorionic gonadotrophin receptor content in the rat.

Pituitary and ovarian function were studied during the loss and recovery of oestrous cyclical activity in rats following treatment with a sustained release formulation of the gonadotrophin-releasing hormone (GnRH) agonist [imidazole benzyl-D-His6,Pro9-ethylamide]-GnRH (histrelin). A single s.c. injection of microencapsulated histrelin (10-300 micrograms peptide/kg) induced a dose-dependent disruption of normal oestrous cyclical activity with a persistent dioestrous-like vaginal cytology. In preliminary studies, pituitary gland stimulation and desensitization were demonstrated when serum LH and FSH levels were greater 1 week after administration of 10 micrograms microencapsulated histrelin/kg compared with 300 micrograms microencapsulated histrelin/kg. Changes in pituitary and ovarian function were assessed over time following injection of microencapsulated histrelin (100 micrograms peptide/kg). LH secretion was maximal within 8 h and then gradually declined, remaining at dioestrous levels from days 7 to 28. Serum oestradiol concentrations remained low and rose above dioestrous levels only on day 28. In contrast, ovarian LH/human chorionic gonadotrophin (LH/hCG) receptor content fell within 8 h and, after a nadir on day 7, slowly returned to dioestrous levels by day 28. The increase in ovarian LH/hCG receptor content preceded any significant change in pituitary gonadotrophin secretion, indicating a differential pattern of recovery for pituitary and ovarian function. Subsequent studies tested the possibility that these temporal differences in pituitary and ovarian function may result from histrelin acting directly on these tissues. Treatment with histrelin microcapsules (300 micrograms peptide/kg) prevented any increase in LH secretion in response to a GnRH challenge 3 days later, indicating a direct action of histrelin on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

3,4-Dihydroxyphenylacetic acid concentrations in the intermediate lobe and neural lobe of the posterior pituitary gland as an index of tuberohypophysial dopaminergic neuronal activity.

Tuberohypophysial dopamine (DA) neurons terminate in the intermediate and neural lobes of the posterior pituitary. The objective of this study was to determine if concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a major metabolite of DA in these regions, reflect the activity of tuberohypophysial DA neurons. The concentrations of DOPAC and DA in the intermediate lobe were approximately twice those in the neural lobe, so that the ratios of DOPAC/DA were similar between lobes. The administration of a monoamine oxidase inhibitor pargyline produced a rapid decline (by 5 min) of DOPAC concentrations in both the intermediate and neural lobes. The administration of nomifensine, an inhibitor of DA uptake at the nerve terminal, produced a modest 33% decline in DOPAC concentrations in the intermediate lobe, but was without effect in the neural lobe. Activation of tuberohypophysial DA neurons by electrical stimulation of the pituitary stalk increased both the rate of DA synthesis (accumulation of dihydroxyphenylalanine (DOPA) after administration of the decarboxylase inhibitor NSD 1015) and the concentrations of DOPAC in the intermediate and neural lobes. Administration of the DA antagonist haloperidol increased, and the DA agonist apomorphine decreased both the rate of DOPA accumulation and DOPAC concentrations in the intermediate lobe but not the neural lobe. The results of the present study demonstrate that: (1) elimination of DOPAC from the intermediate lobe and neural lobe is rapid and alterations in DOPAC concentrations reflect dynamic changes in metabolism of DA; (2) DA which is released and recaptured is a minor contributor to DOPAC concentrations; and (3) alterations in the activity of tuberohypophysial DA neurons are accompanied by corresponding changes in DOPAC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Comparison of the effects of ether and restraint stress on the activity of tuberoinfundibular dopaminergic neurons in female and male rats.

The purpose of the present study was to characterize the acute inhibitory effects of restraint stress on the activity of tuberoinfundibular dopamine (DA) neurons as estimated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence. The time course of the effects of two types of physical restraint (immobilization in the supine position or confinement in an acrylic cylindrical tube) was determined in unanesthetized and diethylether (ether)-exposed female and male rats. The combination of brief (2 min) exposure to ether followed by 10 and 20 min of supine restraint increased concentrations of prolactin in plasma and decreased DOPAC concentrations in median eminence of both female and male rats. Thirty minutes of supine restraint decreased DOPAC concentrations in the median eminence of female rats that were not exposed to ether, and brief exposure to ether enhanced this effect. By contrast, 30 min of supine restraint failed to alter DOPAC concentrations in the median eminence in either unanesthetized or ether-exposed male rats. Tube restraint in the absence of ether failed to alter DOPAC concentrations in the median eminence of either female or male rats; but in female rats preexposed to ether, 30 min of tube restraint decreased DOPAC concentrations in the median eminence. On the other hand, in the absence of physical restraint, 2 min ether exposure caused a transient increase in prolactin secretion and a concurrent decrease of DOPAC concentrations in median eminence of both female and male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗