Pancreatic acini possess endothelin receptors whose internalization is regulated by PLC-activating agents.
Endothelin-1 (ET-1) and ET-3 mRNA have been found in the pancreas. We investigated the ability of ET-1, ET-2, and ET-3 to interact with and alter dispersed rat pancreatic acinar cell function. Radiolabeled ETs bound in a time- and temperature-dependent fashion, which was specific and saturable. Analysis demonstrated two classes of receptors, one class (ETA receptor) had a high affinity for ET-1 but a low affinity for ET-3, and the other class (ETB receptor) had equally high affinities for ET-1 and ET-3. No specific receptor for ET-2 was identified. Pancreatic secretagogues that activate phospholipase C (PLC) inhibited binding of 125I-labeled ET-1 (125I-ET-1) or 125I-ET-3, whereas agents that act through adenosine 3',5'-cyclic monophosphate (cAMP) did not. A23187 had no effect on 125I-ET-1 or 125I-ET-3 binding, whereas the phorbol ester 12-O-tetradecanoylphorbol 13-acetate reduced binding. The effect of cholecystokinin octapeptide (CCK-8) was mediated through its own receptor. Stripping of surface bound ligand studies demonstrated that both 125I-labeled ET-1 and 125I-labeled ET-3 were rapidly internalized. CCK-8 decreased the internalization but did not change the amount of surface bound ligand. Endothelins neither stimulate nor alter changes in enzyme secretion, intracellular calcium, cAMP, or [3H]inositol trisphosphate (IP3). This study demonstrates the presence of ETA and ETB receptors on rat pancreatic acini; occupation of both receptors resulted in rapid internalization, which is regulated by PLC-activating secretagogues. Occupation of either ET receptor did not alter intracellular calcium, cAMP, IP3, or stimulate amylase release.
Hildebrand
P
P
Department of Gastroenterology, University Hospital, Basel, Switzerland.
Mrozinski
J E
JE
Mantey
S A
SA
Patto
R J
RJ
Jensen
R T
RT
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D020109:Devazepide; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001570:Benzodiazepinones; D016232:Endothelins; D017466:Receptors, Endothelin; D012633:Secretin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D002217:Carbachol; D002766:Cholecystokinin; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000681:Amylases; D020109:Devazepide; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin; D015056:1-Methyl-3-isobutylxanthine