Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports have demonstrated that (-)-delta9-tetrahydrocannabinol (delta9-THC) and arachidonylethanolamide [anandamide (AEA)] were able to inhibit prolactin (PRL) secretion from the anterior pituitary gland in male rodents, whereas ovarian phase-dependent effects were seen in females. However, in most of these studies, the analysis of PRL levels was performed at times longer than 30 min after cannabinoid administration. In the present study, we examined the time course of the effects of three different cannabimimetics, delta9-THC, AEA, and AM356 (R-methanandamide), a more stable analog of AEA, on PRL and gonadotrophin secretion in male Wistar rats. In addition, we characterized the presence of cannabinoid receptors in hypothalamic structures related to neuroendocrine control and studied their potential involvement in the effects of cannabimimetics. We found that the three compounds decreased plasma luteinizing hormone (LH) levels, although only the effects of delta9-THC were statistically significant. The inhibitory effect was already apparent at 40 min after administration, but only in the case of delta9-THC did it persist up to 180 min after administration. No significant changes were seen in plasma follicle-stimulating hormone (FSH) levels after the administration of any of the three different cannabimimetics at any of the four times analyzed. Both AEA and AM356 produced a significant decrease in plasma PRL levels, which appeared at 20 min after administration and persisted up to 60 min, waning after this time. Interestingly, the time course of the effect of delta9-THC resembled that of AEA and AM356 only during the later part of the response, because delta9-THC produced a marked increase in plasma PRL levels at 20 min, no changes at 40 min and a decrease from 60 min up to 180 min. In additional experiments, we tried to elucidate which of these two phases observed after delta9-THC administration was mediated by the activation of cannabinoid receptors. These receptors are present in hypothalamic structures related to neuroendocrine control, with the highest densities in the arcuate nucleus (dorsal area) and the medial preoptic area, and the lowest in the lateral hypothalamic area, although none of these regions exhibited high densities for this receptor as compared with classical regions containing cannabinoid receptors, such as the basal ganglia. The activation of these receptors by delta9-THC seems to be involved in the inhibitory phase of the effect of this cannabinoid on PRL release, but not in the early stimulation; when these receptors were blocked with a specific antagonist, SR141716, the stimulation by delta9-THC was still observed, but the late inhibition was abolished. In summary, AEA and AM356 markedly decreased PRL release and slightly decreased LH secretion, with no changes on FSH release. delta9-THC also produced a marked inhibition of LH secretion, but its effects on PRL were biphasic with an early stimulation not mediated by the activation of cannabinoid receptors, followed by a late and cannabinoid receptor-mediated inhibition. Their site of action may well be the hypothalamic structures related to neuroendocrine control, which contain a small, but probably very active, population of cannabinoid receptors.
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PMID:Time course of the effects of different cannabimimetics on prolactin and gonadotrophin secretion: evidence for the presence of CB1 receptors in hypothalamic structures and their involvement in the effects of cannabimimetics. 925 67

Natural and synthetic cannabinoid receptor agonists have been described to exert profound effects on both the neuroendocrine integration and the functional responses of the immune system. In the present study, Wistar rats were exposed to the highly potent cannabinoid agonist HU-210 (1, 5 and 25 microg/kg) during gestation and lactation and the ensuing effects on several endocrine and immune parameters of the adult male offspring were analyzed. Perinatal exposure to HU-210 partially affected the distribution of lymphocyte subpopulations in the spleen and peripheral blood. The major changes observed occur after maternal exposure to the 25 microg/kg dose of HU-210. There was a reduction in the T-helper subpopulation in the spleen and a dose-related decrease in the rate of T(helper)/T(cytotoxic) in peripheral blood lymphocytes. Concanavalin-A and lipopolysaccharide-induced proliferation were normal in all the groups tested. In the same animals, perinatal exposure to HU-210 did not affect basal levels of growth hormone, IGF-1, prolactin, or follicle-stimulating hormone. Basal values of luteinizing hormone were elevated in animals given the 1 microg/kg dose of HU-210. Corticosterone levels were reduced in the animals exposed to the higher dose of HU-210 during gestation and lactation. These animals exhibited a decreased responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis to the stimulation with a single injection of HU-210 (20 microg/kg, i.v.) at adult ages, which may reflect the onset of long-lasting tolerance to the HPA-activating properties of cannabinoids. The opposite pattern of response was found in the animals given the 1 microg/kg dose, in which a sensitization of the corticosterone response to acute HU-210 was observed. The present work reveals that maternal exposure to cannabinoids results in minor changes in the development of the immune system, but may induce long-lasting alterations in the functional status of the HPA axis.
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PMID:Maternal exposure to the synthetic cannabinoid HU-210: effects on the endocrine and immune systems of the adult male offspring. 1060 15