title: Receptors for vasoactive intestinal peptide and secretin on guinea pig pancreatic acini.
abstract: We investigated the abilities of VIP and secretin to occupy receptors and to increase cellular cyclic AMP using dispersed acini from guinea pig pancreas. The dose-inhibition curve for inhibition of binding of 125I-VIP by VIP was broad with detectable inhibition at 0.1 nM VIP, half-maximal inhibition at 2 nM VIP and complete inhibition at 10 microM VIP. Secretin also inhibited binding of 125I-VIP was compatible with two VIP-preferring receptors with one class having a high affinity for VIP (Kd 1.1 nM) and a low affinity for secretin (Kd 5 microM) and the other class having an intermediate affinity for VIP (Kd 470 nM). The dose inhibition curve for inhibition of binding of 125I-secretin by secretin was not broad. Half-maximal inhibition occurred with 7 nM secretin or with 10 microM VIP. Computer analysis was compatible with a single secretin-preferring receptor with a high affinity for secretin (Kd 7 nM) and a low affinity for VIP (Kd 5.9 microM). Comparison of the ability of VIP to increase cyclic AMP with or without the secretin-receptor antagonist, secretin-5-27, demonstrated only occupation of the high affinity VIP-preferring or high affinity secretin-preferring receptors increase cyclic AMP. Our results demonstrate that, in contrast to previous reports, guinea pig pancreatic acini possess 3 classes of receptors that interact with VIP and secretin. The low affinity receptor seen with 125I-VIP is not the same as the secretin-preferring receptor and does not increase cellular cyclic AMP.
authors.forename: Z C
authors.initials: ZC
authors.lastname: Zhou
authors.forename: J D
authors.initials: JD
authors.lastname: Gardner
authors.forename: R T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin / Q000378:metabolism* / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; C029937:secretin receptor; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP