Interaction of peptides related to VIP and secretin with guinea pig pancreatic acini.
The abilities of human and rat growth hormone-releasing factors (hGHRF, rGHRF), peptide histidine isoleucine or methionine (PHI, PHM) and the Gila monster venom peptides (helospectin I, helospectin II, and helodermin) to interact with guinea pig pancreatic acini were characterized and compared with vasoactive intestinal peptide (VIP) and secretin. Each peptide caused a sevenfold stimulation of amylase release, and the relative potencies were: VIP greater than helospectin I = helospectin II = helodermin = rGHRF greater than PHI = PHM greater than hGHRF greater than secretin. Each peptide inhibited 125I-labeled VIP binding, and the relative potencies agreed closely with those for stimulating enzyme secretion. Each peptide inhibited 125I-labeled secretin binding with the potencies: secretin greater than helospectin I = helospectin II = helodermin greater than rGHRF = PHI = VIP greater than PHM greater than hGHRF. Each peptide caused a 78-fold increase in adenosine 3',5'-cyclic monophosphate cAMP. VIP or rGHRF and PHI or PHM demonstrated high and low selectivity, respectively, for VIP receptors, secretin high selectivity for the secretin receptor, and helospectin I or II and helodermin a relatively high affinity for both VIP and secretin receptors. Correlation of the ability of each peptide to increase cAMP or amylase release and inhibit binding of 125I-VIP or 125I-secretin suggested all the actions of these peptides could be explained by the occupation of VIP or secretin receptors. To investigate this further, 125I-labeled helodermin was prepared, and binding was saturable, specific, and could be accounted for by the binding to VIP or secretin receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhou
Z C
ZC
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Gardner
J D
JD
Jensen
R T
RT
D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006168:Guinea Pigs; D008116:Lizards; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010451:Peptide PHI / Q000494:pharmacology; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide; D011994:Recombinant Proteins / Q000494:pharmacology; D012633:Secretin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology
D010451:Peptide PHI; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D011994:Recombinant Proteins; D014688:Venoms; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D013007:Growth Hormone-Releasing Hormone; D000681:Amylases