PACAP and VIP Stimulate Ca2+ Oscillations in Rat Gonadotrophs through the PACAP/VIP Type 1 Receptor (PVR1) Linked to a Pertussis Toxin‐Insensitive G‐Protein and the Activation of Phospholipase C‐β

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Abstract
Pituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are hypothalamic factors that play roles in the regulation of anterior pituitary cell activity. PACAP exists in 2 forms physiologically, a 38 amino acid form (PACAP38) and a form possessing the N‐terminal 27 amino acids of PACAP38 (PACAP27). We have previously shown that PACAP38 stimulates an increase in [Ca2+]i in rat gonadotrophs. In an attempt to identify the PACAP receptor type underlying this effect, we compared the potency of PACAP38, PACAP27 and VIP to stimulate Ca2+ changes in identified single rat gonadotrophs. All 3 peptides at 100 nM were capable of stimulating high amplitude Ca2+ oscillations, which were also observed in the absence of extracellular Ca2+. The order of potency of these peptides was PACAP38>PACAP27>VIP, and a potent antagonist of the PACAP/VIP type II binding site ([4‐Cl‐D‐Phe6, Leu17]‐VIP) failed to block these responses, suggesting that these effects are mediated through a PACAP/VIP type 1 receptor (PVR1). The Ca2+ responses to PACAP38 and VIP were unaffected by overnight treatment of the cells with pertussis toxin (PTX; 250 ng/ml) indicating that these responses are mediated by a PTX‐insensitive G‐protein. Finally, the Ca2+ responses stimulated by PACAP38 and VIP were blocked by the phospholipase C‐β blocker U73122 (5 μM). In summary, PACAP stimulates Ca2+ oscillations in rat gonadotrophs through the activation of the PVR1 linked to a PTX‐insensitive G‐protein and the activation of phospholipase C‐β. VIP can stimulate the same pathway in rat gonadotrophs, although it is at least 100 fold less potent than PACAP38.

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