The effects of a chemically diverse range of calcium channel antagonists on the AVP-stimulated ACTH response in ovine corticotrophs.
Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) release from pituitary corticotrophs by a mechanism dependent on extracellular calcium (Ca2+e). The involvement, in this response, of Ca2+ influx via L-type voltage sensitive Ca2+ channels (VSCC) was studied using cultured ovine anterior pituitary cells. Representatives of 3 chemically distinct classes of organic antagonists of L-type VSCC (methoxyverapamil (D600), nifedipine and diltiazem) and 2 inorganic blocking ions (Cd2+ and Co2+) were used. All of the blockers reduced AVP-stimulated ACTH release, but none caused complete inhibition. ACTH release in response to raised extracellular K+ concentration was also inhibited by these antagonists, with D600 and Cd2+ completely abolishing the response. These results indicate that there is a considerable, but not total, dependence on Ca2+ influx via L-type VSCC during the ACTH response to AVP in ovine corticotrophs.
Department of Zoology, University of Canterbury, Christchurch, New Zealand.
A P
AP
Le Beau
D R
DR
Mason
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D005711:Gallopamil / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay; D012756:Sheep / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D001127:Arginine Vasopressin; D005711:Gallopamil; D003035:Cobalt; D000324:Adrenocorticotropic Hormone; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium