Cyclic AMP-sensitive chloride efflux in rabbit pancreatic acini.
We studied chloride efflux from isolated rabbit pancreatic acini in suspension, by loading with 36Cl to steady state and rapidly washing acini by filtration to determine 36Cl cpm/micrograms DNA remaining. Linear loss of acinar chloride occurred over 5 min (k = 0.038 +/- 0.008 min-1, n = 5). Forskolin (5 x 10(-5) M) increased the rate of chloride efflux (k = 0.100 +/- 0.016 min-1, n = 5, p less than 0.001) 2.6-fold. At 5 min, forskolin increased acinar cAMP levels (1065 +/- 254 versus 7 +/- 2 pmol/mL, n = 5, p less than 0.005) and percentage of chloride efflux (37.4 +/- 2.3 versus 26.0 +/- 2.2%, n = 13, p less than 0.005). The chloride channel inhibitor anthracene-9-carboxylic acid (10(-3) M) had no effect on chloride loss from acini exposed to vehicle (30.9 +/- 1.9 versus 29.9 +/- 2.3%, n = 4), but completely inhibited forskolin-stimulated efflux at 5 min (40.0 +/- 2.4 versus 29.3 +/- 2.4%, n = 5, p less than 0.005). Manipulation of extracellular calcium concentration demonstrated that chloride efflux was not coupled to zymogen granule amylase release. Secretin (10(-7) M) increased acinar cAMP levels (68 +/- 22 versus 7 +/- 2 pmol/mL, n = 5, p less than 0.05) and significantly increased the loss of chloride from acini (34.9 +/- 1.4 versus 26.1 +/- 1.7%, n = 7, p less than 0.005) without affecting amylase release. Secretagogue-stimulated amylase release by cholecystokinin octapeptide (10(-8) M) and carbamylcholine (10(-5) M), did not increase chloride efflux at 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Kopelman
H
H
Department of Pediatrics, Montreal Children's Hospital, Canada.
Gauthier
C
C
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology
D002712:Chlorides; D012633:Secretin; D005576:Colforsin; D002217:Carbachol; D000242:Cyclic AMP; D012844:Sincalide