Acute delta 9-tetrahydrocannabinol exposure alters Ca2+ ATPase activity in neuroendocrine and gonadal tissues in mice.
Acute administration of delta 9-tetrahydrocannabinol (THC) (50 mg/kg) at puberty (35-40 days) significantly (P less than 0.05) reduced Ca2+ ATPase activity in hypothalamic plasma membranes but increased, although not significantly, enzyme activity in hypothalamic tissue obtained from adult mice. In contrast, testicular Ca2+ ATPase activity was increased in pubertal THC-treated males, and significantly reduced in adults. Pituitary Ca2+ ATPase activity exhibited a dose-related decrease after acute THC administration at 0.5, 5 or 50 mg/kg, but there were no differential effects of age. Pituitary plasma membranes obtained from THC-treated males did not respond to in vitro exposure to luteinizing hormone releasing hormone (LHRH, 10(-7) M) with the marked reduction (approximately 40%) in Ca2+ ATPase activity observed in pituitaries from oil-treated controls. In addition, effects of THC appear specific for Ca2+ ATPase activity, since Mg2+ ATPase and Na+/K+ ATPase activities were not affected. These findings indicate that acute in vivo administration of THC influences Ca2+ membrane transport, in particular Ca2+ ATPase activity. These effects occur at each level of the hypothalamic-pituitary-gonadal (HPG) axis, are related to dose and developmental age at exposure, and also appear specific for Ca2+-dependent ATPase activity. Furthermore, THC exposure modulates pituitary sensitivity to LHRH receptor-mediated effects on Ca2+ ATPase activity. Therefore, effects on Ca2+ membrane transport may be involved in acute THC actions on hormonal activity at these HPG sites.
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000032:analysis*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D010902:Pituitary Gland / Q000187:drug effects* / Q000201:enzymology; D012741:Sexual Maturation; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013737:Testis / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors
D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone; D013759:Dronabinol; D007986:Luteinizing Hormone; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium