Ouabain- and potassium-induced stimulation of amylase release in fragments and acini of rabbit pancreas.
Ouabain increases the enzyme secretion from the isolated rabbit pancreas and pancreatic fragments, but not from isolated pancreatic acini. The increase occurs after a delay of 45-60 min and is not accompanied by an increase in lactate dehydrogenase release. The stimulatory effect of ouabain (10(-5) M) is dependent on the presence of extracellular calcium, and is not antagonized by 10(-4) M atropin, 10(-4) M propranolol, 10(-5) M phentolamine, 10(-3) M dibutyryl-cyclic GMP, 10(-6) M tetrodotoxin, 10(-4) M verapamil or 10(-4) M D-600. Elevation of the extracellular potassium concentration to 120 mM in the presence of 10(-4) M atropin also increases the enzyme secretion from rabbit pancreatic fragments. The increase is again dependent on the presence of extracellular calcium and is resistant to adrenergic blockade and to tetrodotoxin, verapamil or D-600. Forskolin also stimulates a Ca2+-dependent release of amylase from pancreatic fragments but not from pancreatic acini. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IMX), ouabain (10(-5) M) and K+ (120 mM) cause an immediate increase in the cyclic AMP content of pancreatic fragments which does not occur in the absence of extracellular calcium. In pancreatic acini, the cAMP production is only slightly increased by ouabain. In the absence of IMX, the cAMP levels in fragments or acini are not detectably altered by ouabain or K+. The results suggest that the stimulation of enzyme secretion by ouabain and high K+ is an indirect effect, mediated by the release of an endogenous transmitter from non-cholinergic, non-adrenergic nerves in the intact preparations. The release and/or the effect of the transmitter appears to be mediated primarily by Ca2+ and secondarily by cyclic AMP.
G A
GA
Kuijpers
I G
IG
van Nooy
J J
JJ
de Pont
D000262:Adenylyl Cyclases / Q000378:metabolism; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits
D004224:Diterpenes; D005576:Colforsin; D010042:Ouabain; D000242:Cyclic AMP; D000681:Amylases; D000262:Adenylyl Cyclases; D011188:Potassium; D002118:Calcium