Effect of SNI-2011 on amylase secretion from parotid tissue in rats and in neuronal nitric oxide synthase knockout mice.
The effect of (+/-)cis-2-methylspilo(1,3-oxathiolane-5,3')quinuclidine (SNI-2011) on the secretory pathway of amylase in parotid tissues was investigated. SNI-2011-induced exocytosis was inhibited by a cell-permeable Ca(2+) chelator or inhibitors of calmodulin kinase II, neuronal nitric oxide synthase (nNOS), soluble guanyl cyclase, cyclic GMP-dependent protein kinase (PKG), and myosin light chain kinase, suggesting that these enzymes were coupled with the exocytosis. Stimulation with SNI-2011 of isolated rat parotid acinar cells loaded with 4,5-diaminofluorescein/diacetate (DAF-2/DA) induced a fast increase in DAF fluorescence corresponding to an increase in the NO production. SNI-2011-induced amylase secretion from parotid tissues in nNOS knockout mice has not been observed yet in spite of the expression of muscarinic M(3) receptors and the maintenance of secretory response to isoproterenol in the tissues. These results indicate the implication of the activation of Ca(2+)- and calmodulin-dependent enzymes and NOS-PKG signaling pathway in SNI-2011-induced amylase secretion from parotid acinar cells.
Yuan
Zhenfang
Z
Department of Pharmacology, Tokushima University School of Dentistry, Kuramoto-cho, Tokushima City, Japan.
Iida
Hirokazu
H
Inoue
Noriko
N
Ishikawa
Yasuko
Y
Ishida
Hajime
H
D000470:Alkaloids / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002227:Carbazoles; D002614:Chelating Agents / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005838:Genotype; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010069:Oxadiazoles / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011758:Pyrroles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D000096926:Benzenesulfonamides
D000470:Alkaloids; D000681:Amylases; D001381:Azepines; D001565:Benzoates; D001596:Benzylamines; D002118:Calcium; D002121:Calcium Channel Blockers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002217:Carbachol; D002227:Carbazoles; D002614:Chelating Agents; D017869:Cyclic GMP-Dependent Protein Kinases; D004533:Egtazic Acid; D004791:Enzyme Inhibitors; D004963:Estrenes; D005707:Gallic Acid; D006162:Guanylate Cyclase; D007093:Imidazoles; D007211:Indoles; D008981:Molsidomine; D018721:Muscarinic Agonists; D009219:Myosin-Light-Chain Kinase; D019331:NG-Nitroarginine Methyl Ester; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D010069:Oxadiazoles; D010396:Penicillamine; D010726:Phosphodiesterase Inhibitors; D010862:Pilocarpine; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011760:Pyrrolidinones; D011810:Quinoxalines; D011812:Quinuclidines; D013449:Sulfonamides; D013876:Thiophenes; D010738:Type C Phospholipases; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C110881:S-nitro-N-acetylpenicillamine; C056218:ML 9; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C073601:KT 5823; C072105:KN 93; D000096926:Benzenesulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; C057416:KT 5720; C002385:linsidomine; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; C059240:cevimeline