Characterization of gastrin receptors on guinea pig pancreatic acini.
Recent studies have demonstrated gastrin receptors in some pancreatic tumors and that gastrin is a potent stimulant of pancreatic Na+-H+ exchange. In the present study we used 125I-labeled gastrin (125I-gastrin) to characterize gastrin receptors on guinea pig pancreatic acini. Binding of 125I-gastrin was temperature dependent, saturable, and specific for gastrin-related peptides. Analysis demonstrated a single class of receptors with high affinity for gastrin (Kd = 1.5 nM) and a binding capacity of 1 fmol/mg protein. Binding of 125I-gastrin was inhibited with the following relative potencies (Kd): cholecystokinin octapeptide (CCK-8) (0.35 nM) greater than gastrin-17-I = gastrin-34-I (1.5 nM) greater than pentagastrin (7 nM) greater than desulfated [des(SO3)]CCK-8 (28 nM) greater than CCK-4 (508 nM) and by the receptor antagonists CBZ-CCK-27-32-NH2 (3.5 microM) greater than proglumide analogue 10 (30 microM) greater than asperlicin (265 microM) greater than Bt2-guanosine 3',5'-cyclic monophosphate (828 micron). In contrast, for both stimulation of enzyme secretion and inhibition of binding of 125I-CCK-8 the relative potencies were CCK-8 much greater than des(SO3)CCK-8 greater than gastrin-17-I = gastrin-34-I greater than pentagastrin greater than CCK-4. For each receptor antagonist the dose-inhibition curve for gastrin-stimulated amylase release was superimpossible with that for CCK-8-stimulated amylase release. Gastrin-17-I at concentrations less than 0.1 microM did not potentiate carbachol or vasoactive intestinal peptide-stimulated amylase secretion and did not affect basal or stimulated adenosine 3',5'-cyclic monophosphate or 45Ca outflux.(ABSTRACT TRUNCATED AT 250 WORDS)
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D005755:Gastrins / Q000502:physiology*; D006168:Guinea Pigs; D006728:Hormones / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000502:physiology*; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000378:metabolism; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005755:Gastrins; D006728:Hormones; D011949:Receptors, Cholecystokinin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000681:Amylases; D012844:Sincalide; D002118:Calcium