The role of calmodulin in rat parotid amylase secretion: effects of calmodulin antagonists on secretion and acinar cell structure.
Using dispersed rat parotid cells, the effects of three calmodulin antagonists, trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7), and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), on amylase release and acinar cell structure were examined. TFP and W-7 strongly inhibited both isoproterenol (ISO)- and dibutyryl cyclic AMP-stimulated amylase release at a concentration of 50 or 100 microM, while W-5, a weak calmodulin antagonist, had only little effect. Cyclic AMP level was markedly elevated by ISO even in the presence of TFP or W-7. These results indicate that the calmodulin antagonists affect amylase release at steps distal to cyclic AMP metabolism. Electron micrographs demonstrated that treatment of parotid cells with either TFP or W-7 caused a loss of luminal microvilli and surface folds. When cells were stimulated by ISO in the presence of TFP or W-7, the enlarged lumina did not recover to their original size and the discharged secretory material was retained in the lumina. Numerous secretory granules remained in the acinar cytoplasm. W-5 affected the acinar cell structure only a little. These observations lead to the assumption that TFP and W-7 interfered with the normal functions of the cytoskeletal system. It is proposed that calmodulin may be involved in the exocytosis of parotid amylase through the regulation of the cytoskeletal system.
Tojyo
Y
Y
Department of Dental Pharmacology, School of Dentistry, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Matsumoto
Y
Y
Okumura
K
K
Kanazawa
M
M
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D010306:Parotid Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D014665:Vasodilator Agents; D014268:Trifluoperazine; D003994:Bucladesine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D002217:Carbachol; D000242:Cyclic AMP; D000681:Amylases; D007545:Isoproterenol