Effects of inhibitors of intracellular messenger systems on amylase release from rat parotid gland.
Effects of a series of novel inhibitors of calmodulin or protein kinases on amylase release were studied in rat parotid slices. Amylase release induced by a cholinergic agonist, carbamylcholine, was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, 1-(5-chloronaphthalen-1-sulfonyl)-1H-hexahydro-1, 4-diazepine (ML-9), a myosin light chain kinase (MLCK) inhibitor, and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of Ca(2+)-activated, phospholipid-dependent protein kinase (protein kinase C), while N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8), an inhibitor of cyclic AMP-dependent protein kinase (protein kinase A), did not inhibit the release. On the other hand, amylase release induced by a beta-adrenergic agonist, isoproterenol, was inhibited only by H-8, but not by W-7, ML-9 or H-7. These results suggest that cholinergic stimulation evokes amylase release via the Ca(2+)-dependent system which involves calmodulin, MLCK and protein kinase C, while beta-adrenergic stimulation via the cyclic AMP-dependent system involves protein kinase A.
Hashioka
T
T
Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Kato
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D005089:Exocytosis; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010306:Parotid Gland / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology
D001381:Azepines; D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C056218:ML 9; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D009219:Myosin-Light-Chain Kinase; D000681:Amylases