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PACAP and VIP Stimulate Ca 2+ 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
Author(s) -
Hezareh Marjan,
Schlegel Werner,
Rawlings Stephen R.
Publication year - 1996
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1996.04645.x
Subject(s) - pertussis toxin , medicine , endocrinology , receptor , chemistry , g protein , gonadotropic cell , toxin , biology , pituitary gland , biochemistry , hormone
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 [Ca 2+ ] 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 Ca 2+ changes in identified single rat gonadotrophs. All 3 peptides at 100 nM were capable of stimulating high amplitude Ca 2+ oscillations, which were also observed in the absence of extracellular Ca 2+ . 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‐Phe 6 , Leu 17 ]‐VIP) failed to block these responses, suggesting that these effects are mediated through a PACAP/VIP type 1 receptor (PVR1). The Ca 2+ 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 Ca 2+ responses stimulated by PACAP38 and VIP were blocked by the phospholipase C‐ β blocker U73122 (5 μM). In summary, PACAP stimulates Ca 2+ 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.