Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phencyclidine (PCP) has been found to affect neuroendocrine function by altering the release of the anterior pituitary hormones, adrenocorticotrophin, luteinizing hormone and prolactin. The purpose of this study was to examine the effect of PCP on release of the two pituitary hormones also derived from the adrenocorticotropin precursor, namely, alpha-melanocyte-stimulating hormone and beta-endorphin (beta-E), synthesized in the neurointermediate and anterior lobes of the pituitary. At behaviorally active doses, PCP administered i.c.v. increased plasma levels of immunoreactive beta-E (i beta-E) without affecting the concentration of immunoreactive alpha-melanocyte-stimulating hormone, suggesting that PCP increased the release of beta-E from only the anterior lobe of the pituitary. Dexamethasone pretreatment blocked the PCP-induced increase in i beta-E which indicated further the anterior lobe effects of PCP. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate), a selective PCP ligand, at behaviorally active doses also increased the plasma concentration of i beta-E. The dose-response curves for induction of behavior was very different from that for increasing the concentration of i beta-E in plasma. The increase in release of i beta-E was stereoselective as (+)-(1-(1-phenylcyclohexyl)-3 methylpiperidine but not (-)-(1-(1-phenylcyclohexyl)-3 methylpiperidine increased release of i beta-E. The increase in plasma levels of beta-E was not due to an interaction with opioid receptors because naloxone did not block PCP-induced release of beta-E. In vitro, PCP also significantly increased release of i beta-E from anterior lobe of the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phencyclidine increased release of beta-endorphin from anterior lobe of the pituitary. 165 42

Phencyclidine (PCP) markedly stimulates the pituitary-adrenal axis in the rat, inducing the release of adrenocorticotropin (ACTH) and corticosterone. However, the site or sites where PCP produces these effects is not known. This study sequentially examined the effects of PCP on the different components of the central nervous system-pituitary-adrenal axis. PCP did not produce corticosterone release in dispersed adrenal cells in vitro, nor did it stimulate the release of corticosterone in hypophysectomized rats, showing that PCP-induced corticosterone release in intact animals is secondary to the release of ACTH from the pituitary. PCP failed to alter either the basal or the corticotropin releasing factor-induced release of ACTH from superfused pituitaries in vitro, indicating that PCP does not act directly at the level of the pituitary. PCP increased plasma levels of ACTH in adrenalectomized rats, demonstrating that PCP does not stimulate the release of ACTH only by blocking glucocorticoid negative feedback mechanisms. PCP stimulated the release of both ACTH and corticosterone when given by injection directly into brain via the lateral cerebral ventricles. These results indicate that PCP activates the pituitary-adrenal axis by acting at a site or sites within the central nervous system, leading to the subsequent release of ACTH from the pituitary.
 ...
PMID:Determination of the loci of action of phencyclidine on the CNS-pituitary-adrenal axis. 216 1

Phencyclidine (PCP) is a widely used drug of abuse; however, little is known of its effects on neuroendocrine function. The present study characterized the effects of the acute and chronic administration of PCP on the release of adrenocorticotropin, corticosterone and prolactin in the rat. For the acute studies, PCP hydrochloride (0.5-10.0 mg/kg s.c.) was administered and the subjects were sacrificed 15 to 300 min later. The acute administration of PCP produced rapid and long-lasting increases in plasma levels of adrenocorticotropin and corticosterone but decreased plasma levels of prolactin. For the chronic studies, PCP (1.0-20.0 mg/kg/day s.c.) was injected daily and the subjects sacrificed 60 min after injection on day 15. PCP continued to stimulate the pituitary-adrenal axis after chronic administration; however, there was a decrease in the magnitude of response, indicating the development of some degree of tolerance. In contrast, none of the doses of PCP tested decreased plasma prolactin levels in chronically treated subjects. There were no differences in plasma or brain levels of PCP in the chronically PCP-treated rats, indicating that tolerance was not due to changes in the biodisposition of PCP. These results indicate that PCP disrupts neuroendocrine function markedly in the rat. The differential development of tolerance to the effects of PCP on the pituitary-adrenal axis and prolactin release may indicate that different neurochemical substrates underlie the effects of PCP on different endocrine systems.
 ...
PMID:Characterization of the effects of the acute and chronic administration of phencyclidine on the release of adrenocorticotropin, corticosterone and prolactin in the rat: evidence for the differential development of tolerance. 254 36

It is suggested that the antipsychotic efficacy of opioids in patients suffering from schizophrenia may result from an interaction of opioids with the dopaminergic system. The modulatory effect of opioids on dopaminergic functions has already been demonstrated in basic experiments: Anatomical and biochemical data reveal an interaction between opioid receptors and dopamine (DA) actions on dopaminergic nerve terminals, cell bodies, and afferent nerve endings. Endogenous enkephalin levels correlate well with the endogenous dopamine content in various brain areas. Systemic or iontophoretic administration of morphine alters the spontaneous activity of ventral tegmental dopaminergic neurons. Morphine and enkephalin effectively enhance pituitary prolactin release, whereas dopamine inhibits it. Opioid agonists effectively alter DA release, DA reuptake, and DA metabolism in the striatum and substantia nigra. In reverse, chronic neuroleptic treatment enhances the synthesis and release of pituitary beta-endorphin. Opioids affect contralateral rotation elicited by dopamine agonists in animals with unilateral lesions of the nigrostriatal pathway. Phencyclidine, a psychotropic drug that shares certain pharmacological characteristics with the putative sigma-opioid receptor ligand SKF 10,047, indirectly mimics the effects of dopamine agonists on prolactin release, release of acetylcholine, etc. It is suggested that an imbalance of opiate-DA interaction might be involved in the pathogenesis of schizophrenia. Consequently, clinical studies on the effects of opioids on psychotic symptoms should also examine opioid influence on dopaminergic functions in these patients.
 ...
PMID:Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia. With special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia. 299 42

Phencyclidine (PCP) activates the hypothalamo-pituitary-adrenal (HPA) axis and decreases plasma prolactin levels in the rat. PCP is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, but it also inhibits the reuptake of dopamine, serotonin and norepinephrine. The purpose of the present study was to utilize the PCP analogue N-[1-(2-thienyl)cyclohexyl]piperidine; (TCP), the potent dopamine reuptake inhibitor N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine; (BTCP) and the nonselective monoamine reuptake inhibitor cocaine as pharmacologic probes in order to determine the roles of noncompetitive NMDA receptor blockade and inhibition of dopamine reuptake in the neuroendocrine effects of PCP. PCP, TCP and cocaine increased plasma levels of adrenocorticotropin and corticosterone, but BTCP had no effect. In contrast, PCP, BTCP and cocaine decreased plasma prolactin, but TCP produced no such effect. The data suggest that mechanisms besides inhibition of dopamine reuptake are involved in the effects of PCP on the HPA axis, and the PCP-induced decrease in plasma prolactin is not a consequence of inhibition of NMDA receptor-mediated neurotransmission.
 ...
PMID:The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition of the dopamine reuptake in the neuroendocrine effects of phencyclidine. 1628 27