The effects of a chemically diverse range of calcium channel antagonists on the AVP-stimulated ACTH response in ovine corticotrophs

Abstract

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) release from pituitary corticotrophs by a mechanism dependent on extracellular calcium (Ca 2+ e). The involvement, in this response, of Ca 2+ influx via L-type voltage sensitive Ca 2+ 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 (Ca 2+ and Co 2+) 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 Ca 2+ completely abolishing the response. These results indicate that there is a considerable, but not total, dependence on Ca 2+ Influx via L-type VSCC during the ACTH response to AVP in ovine corticotrophs.