CGRP-INDUCED ACTIVATION OF K-ATP CHANNELS IN FOLLICULAR XENOPUS OOCYTES

The two-microelectrode voltage-clamp technique was used to monitor K+ channel activity in Xenopus oocyte follicular cells, which are electrically coupled to the oocyte itself by gap junctions. Endogenous vasodilators such as calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), prostaglandin E(2) (PGE(2)) and adenosine activate glibenclamide-ATP-sensitive K+ (K-ATP) channels in Xenopus oocyte follicular cells. The mechanism of action of CGRP was studied in detail. CGRP effects undergo a rapid desensitization. CGRP acts via CGRP(1) receptors. Its effects are antagonized by the amino-truncated CGRP analog hCGRP(8-37). The second messenger for CGRP activation of K-ATP channels is cAMP. Phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine enhances the CGRP response while adenyl cyclase inhibition by either 2',5'-dideoxyadenosine or progesterone nearly completely depresses the CGRP response. Vasoconstrictors such as ACh and angiotensin II also have receptors in follicular cells. ACh strongly inhibits the CGRP activation of K+ channels as it inhibits the activation of K-ATP channels by P1060, but angiotensin II does not. It is concluded that as in vascular smooth muscle cells, CGRP and probably other hyperpolarizing vasodilators open K-ATP channels in follicular cells by protein kinase A activation.