Effects of synthetic cyclic AMP analogs on amylase exocytosis from rat pancreatic acini.
Diastereomers of adenosine 3',5'-phosphorothioate activate cAMP-dependent protein kinases (cAMP-PK) in vitro. We found that these compounds are highly selective tools to monitor cAMP-dependent PKA activation and its effect on amylase exocytosis from pancreatic acini. In permeabilized rat acinar cells, (Sp)-cAMPS dose-dependently stimulated amylase secretion, while (Rp)-cAMPS inhibited (Sp)-cAMPS-induced amylase release. In intact rat acini, 8-Br-(Rp)-cAMPS reduced the secretory responses to secretin, vasoactive intestinal polypeptide (VIP), 8-Br-cAMP, and 8-Br-(Sp)-cAMPS, but not to cerulein. Another derivative, dibutyryl-(Rp)-cAMPS, induced a small inhibitory effect against 8-Br-(Sp)-cAMPS and VIP, which was overlapped by an unspecific stimulatory effect on amylase exocytosis induced by the degradation product butyrate. Furthermore, (Sp)-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'- monophosphorothioate ((Sp)-5,6-DCl-cBIMPS), a specific cAMP-PK activator, induced a maximal induction of cAMP-PK activity, but its stimulation of amylase secretion was less than that by secretin. (Sp)-5,6-DCl-cBIMPS regulated the phosphorylation of several proteins, which were also affected by secretin. However, secretin had additional effects. Its action was most likely mediated by a dual effect on the cAMP and the calcium pathway. Our results indicate that the cAMP-dependent pathway is involved in amylase exocytosis from rat pancreatic acini.
Schäfer
C
C
Department of Internal Medicine, Philipps-University of Marburg, Germany.
Steffen
H
H
Printz
H
H
Göke
B
B
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012633:Secretin / Q000378:metabolism; D013237:Stereoisomerism
D010750:Phosphoproteins; D012633:Secretin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000681:Amylases; D002118:Calcium