Soluble guanylyl cyclase is localised in the acinar cells and participates in amylase secretion in rat parotid gland.
It is well known that the muscarinic cholinergic agonists, carbachol and methacholine, enhance nitric oxide synthase (NOS) activity, and also stimulate salivary secretion. In the present study, we investigated whether salivary secretion by muscarinic cholinergic stimulation is mediated through the NO/cGMP signaling pathway in rat salivary glands. Since NO activates soluble guanylyl cyclase (sGC) and cGMP may function as a mediator, the localisation of sGC was investigated in the salivary glands. sGC was localized in both the acinar and duct cells of the rat parotid and sublingual glands, and localized only in the acinar cells of the submandibular glands. S-Nitroso-glutathione (NO generator; GSNO) and YC-1 (NO-independent sGC activator) stimulated sGC in the cytosol to synthesise cGMP. The combination of GSNO and YC-1 stimulated sGC synergistically. Carbachol, GSNO and YC-1 enhanced amylase release from the rat parotid glands. Amylase release stimulated by carbachol and GSNO was inhibited by addition of the sGC inhibitor, ODQ, and cGMP-dependent protein kinase inhibitor, KT-5823. These results indicate that amylase release may be mediated through the NO/cGMP signaling pathway.
Department of Biochemistry, The Nippon Dental University at Niigata, 1-8 Hamaura-cho, 951-8580, Japan. hshimo@ngt.ndu.ac.jp
Hiromi
H
Shimomura
Satoshi
S
Tanaka
Nobuhiro
N
Komine
Shohachi
S
Shimooka
Akane
A
Imai
Tomoko
T
Nashida
D000681:Amylases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000032:analysis* / Q000037:antagonists & inhibitors; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D020536:Enzyme Activators; D007191:Indazoles; D018721:Muscarinic Agonists; D020030:Nitric Oxide Donors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D002217:Carbachol; D000681:Amylases; D006162:Guanylate Cyclase; D006152:Cyclic GMP