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Biomedical subjects

L Grandison

Publications and source records attributed to L Grandison.

35 records · Page 2Linked to original sources
PubMed1982

Effect of naltrexone on regional brain oxygen consumption in the cat.

Cerebral blood flow was measured by 141Ce and 85Sr microsphere accumulation, and oxygen saturation of arterial and venous blood within 9 regions of the brain was determined by microspectrophotometric measurement in chloralose anesthetized cats. Extraction was calculated as the difference between oxygen content of arterial and venous blood. Oxygen consumption was computed as the product of blood flow and oxygen extraction. Global and regional comparisons were made between 7 anesthetized cats and 7 anesthetized cats given 1 mg/kg naltrexone HCl i.v. Naltrexone treatment reduced total brain oxygen consumption by 48% at 20 min after intravenous injection. Analysis of the anterior and posterior cortex, lenticulate nuclei, hippocampus, thalamus, hypothalamus, medulla, pons and cerebellum indicated that the oxygen consumption of the pons and hypothalamus was reduced to the greatest extent. The decreased oxygen consumption reduced blood flow in the whole brain, and the pons. The oxygen supply to consumption ratio was not altered by naltrexone except in the hypothalamus where an even greater excess of oxygen was delivered. These observations are interpreted as indicating that opiate receptor blockade is associated with reduced brain metabolism and that this response is not restricted to regions of high opiate receptor concentration.

Animals↗
PubMed1982

Suppression of prolactin secretion by benzodiazepines in vivo.

Administration of benzodiazepines to male or female rats was observed to inhibit prolactin release. Basal secretion of prolactin was only slightly suppressed with the highest dose of benzodiazepines; however, the rise in prolactin release following a stimulus was prevented even at low doses (0.1-1 mg/kg). The benzodiazepine diazepam blocked stress-induced prolactin release and, when given during the critical period of proestrus, the proestrus surge of prolactin. Diazepam administration also blunted the release of prolactin induced by dopaminergic receptor blockade following haloperidol, or by serotonergic receptor activation produced by fluoxetine, a serotonergic reuptake inhibitor plus 5-hydroxytryptophan, a serotonin precursor. Inhibition of prolactin release by benzodiazepine was dose related, and inhibition was still evident after repeated diazepam injection. The potency of three benzodiazepine analogues to inhibit prolactin release correlated with their potency to displace radiolabeled diazepam binding from brain membrane fractions or to induce other biological responses (clonazepam greater than diazepam greater than chlordiazepoxide). These actions of benzodiazepines on prolactin release are similar to those reported for gamma-aminobutyric acid (GABA). The hypothesis of a benzodiazepine GABA receptor complex suggests that GABA may be involved in these in vivo actions of diazepam.

5-Hydroxytryptophan↗
PubMed1982

gamma-Aminobutyric acid- and benzodiazepine-binding sites in human anterior pituitary tissue.

The existence of a gamma-aminobutyric acid (GABA) system in human anterior pituitary tissue was examined. Crude membrane fractions prepared from human anterior pituitary tissue bound tritiated GABA. The binding was saturable, and Scatchard analysis indicated a single binding site of high affinity (Kd = 40 nM) and a maximum binding of 1.2 pmol/mg protein. Binding was displaced in a dose-related manner by the GABA agonists muscimol (KI = 1 X 10(-8) M), isoguvacine (KI = 6 X 10(-7) M), THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol); KI = 5 X 10(-6) M), and the antagonist (+)bicuculline (KI = 5 X 10(-5) M) but not its inactive stereoisomer (-)bicuculline (KI greater than 10(-3) M). In anterior pituitary tissue, a significant concentration of GABA was found (mean, 2.5 +/- 0.5 nmol/mg protein) but no glutamic acid decarboxylase activity, the enzyme synthesizing GABA, was detected using a highly sensitive assay. In addition, benzodiazepine binding was present. An affinity of approximately 15 nM and a Bmax of approximately 0.75 pmol/mg protein were observed when using [3H]diazepam as the ligand. No saturable clonazepam binding occurred, and only slight GABA stimulation of diazepam binding was observed (mean, 18%; range, 6-38%). The ability of GABA and benzodiazepine to alter PRL secretion in rats suggests that the human pituitary GABA-binding sites described here might also mediate effects on PRL release.

Adult↗
PubMed1977

Inhibition by prolactin of post-castration rise in LH.

Castration of male and female rats resulted in a marked rise in serum LH. The rise in serum LH was partially or completely prevented by injection of prolactin (Prl), by implantation of a small amount of Prl in the median eminence (ME), by grafting 2 anterior pituitaries (APs) underneath the kidney capsule, or by transplantation of a Prl-secreting pituitary tumor underneath the skin. The larger pituitary tumor transplants secreted more Prl and were more effective in reducing LH release than the smaller tumors which secreted less Prl. Suppression of LH release generally was greater during the earlier than in the later phases of the different treatments. The pituitary LH response to synthetic LH-RH was the same in ovariectomized rats with or without pituitary grafts, and the decrease in hypothalamic LH-RH after orchidectomy was prevented by pituitary grafts. These results indicate that Prl can depress LH release after castration and that these effects are mediated via the hypothalamus.

Animals↗
PubMed1976

Reduced luteinizing hormone release by synthetic luteinizing hormone-releasing hormone (LHRH) in postpartum lactating rats.

The ability of the pituitary to release LH in response to synthetic LHRH was tested in lactating female rats on days 7 and 17 post partum, and compared with that of normal cycling female rats on diestrous day 2 (controls). Three consecutive injections of LHRH (100 ng/100 g BW, sc), each 50 min apart, were given to each rat and sequential blood samples were collected at 25-min intervals by cardiac puncture under light ether anesthesia. In all 3 groups, the 2nd and 3rd injections of LHRH produced much greater increases in serum concentrations of LH than the 1st injection. However, this self-priming effect of LHRH on LH response was markedly attenuated in the postpartum lactating rats (PPL), compared with the normal cycling female rats on diestrous day 2. Three consecutive injections of LHRH produced significantly less LH release in PPL rats than in normal cycling female rats on diestrous day 2. Both day 7 and day 17 PPL rats released equally small amounts of LH in response to LHRH administration. The total amount of LH released by anterior pituitaries (APs) during a 5 h incubation in medium-199, from day 7 or day 17 in PPL rats, was significantly less than that released by the APs from normal cycling female rats on diestrous day 2. APs from day 7 and day 17 PPL rats also released less LH in vitro in response to LHRH (50 ng) stimulation than APs from normal cycling female rats. When APs from normal cycling female rats on diestrous day 2 were incubated with LHRH, the increments in LH release were greater at the end of the 2nd and 3rd h than after the 1st h of incubation. However, such increments in LH release were relatively small when APs from day 7 or day 17 PPL rats were similarly incubated with LHRH.

Animals↗
PubMed1976

Evidence for adrenergic mediation of cholinergic inhibition of prolactin release.

Pilocarpine, a cholinergic agonist, significantly reduced the high levels of serum prolactin in estrogen-primed male rats and in female rats on the late afternoon of proestrus. In male rats treated with reserpine, chlorpromazine, haloperidol, or pimozide, serum prolactin levels were greatly elevated. Subsequent treatment with pilocarpine failed to reduce serum prolactin concentrations in these rats. When atropine, a cholinergic antagonist, was injected ip in doses of 3 to 250 mg/kg into male rats, prolactin release was not altered. However, when atropine was injected prior to pilocarpine, it prevented the reduction in serum prolactin by the latter drug. Methyl-atropine, which does not enter the CNS, did not prevent pilocarpine from inhibiting prolactin release. These results suggest that cholinergic inhibition of prolactin release is mediated via adrenergic neurons, and thus support a role for a cholinergic link in hypothalamic regulation of prolactin release.

Animals↗
PubMed1976

Relation between prolactin and gonadotrophin secretion in post-partum lactating rats.

In post-partum lactating rats, sucking by the young was associated with high prolactin release and maintenance of lactation but severe inhibition of LH and FSH release and suspension of oestrous cycles. Shortly after the pups were removed on day 22 post partum LH and FSH release returned to normal and oestrous cycles resumed. Twice-daily injections of ergocornine methanesulphonate (ERG) into mothers beginning at 5 or 7 days post partum, resulted in sustained inhibition of prolactin release and diminished mild secretion. By frequent exchange of pups between control and ERG-treated mothers, it was possible to maintain vigorous sucking and almost normal pup growth despite low serum prolactin levels and diminished lactation. In these rats, serum levels of LH remained low during 11 or more days of treatment with ERG, but serum FSH was consistently higher than in untreated control mothers. After 11 or more days of ERG treatment, most rats showed a return to normal LH and FSH release and resumption of oestrous cycles. These results suggest (a) that the sucking stimulus rather than high prolactin levels in the circulation is mainly responsible for inhibition of LH and FSH release during the first 11 days post partum, (b) that the sucking stimulus acts to increase prolactin and inhibit LH release by separate hypothalamic mechanisms, and (c) that administration of ERG results in diminished prolactin release and lactation, and in increased release of FSH and subsequently of LH with earlier resumption of oestrous cycles.

Animals↗
PubMed1976

Stimulation of prolactin release in rats by GABA.

Infusion of GABA into the lateral ventricle of intact female rats on the morning of proestrus and in ovariectomized rats significantly stimulated PRL release. This response apparently is not mediated through a direct action on the pituitary since injection of GABA into hypophysectomized rats with a pituitary transplant under the kindney capsule did not alter serum prolactin levels. These observations suggest that GABA may have a role in regulating prolactin secretion.

Aminobutyrates↗