Studies of muscarinic receptor subtypes in salivary gland function in anaesthetized rats

The in vivo study aimed to examine whether muscarinic receptor subtypes other than muscarinic M-3 receptors exert exocrine functional roles in the rat salivary glands. The effects of pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were examined on secretion from the major salivary glands evoked by acetylcholine (0.001 -10 mumol kg(-1) i.v.) in pentobarbitone-anaesthetized rats. Observations were occasionally made on glandular blood flow. 4-DAMP (0.1 -100 nmol kg(-1) i.v.) markedly and equipotently inhibited the acetylcholine-evoked fluid responses in all glands. Pirenzepine (0.1 mumol kg(-1) i.v.-10 mmol k(-1) i.v.) showed significantly lower inhibitory potency than 4-DAMP, most conspicuously in the parotid, while methoctramine (0.1 mumol kg(-1) i.v.-10 mmol kg(-1) i.v.) excited an even lesser inhibitory effect. Also against acetylcholine-evoked blood flow increases, 4-DAMP showed a conspicuous potency. At 1 and 10 mumol kg(-1) i.v. of pirenzepine, the antagonist reduced the protein concentration in the submandibular saliva, but not in the parotid saliva. While 4-DAMP (1 and 10 nmol kg(-1) i.v.) significantly inhibited acetylcholine-evoked protein secretory responses in the submandibular glands, methoctramine (below 10 mumol kg(-1) i.v.) affected the responses in neither gland. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by Y-omega-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.p.), while L-NAME had no or only minute effects on the parotid protein secretion. Thus, in addition to muscarinic M-3 receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular and sublingual glands, While these other receptors are muscarinic M, receptors in the sublingual gland, they may be a different subtype, possibly muscarinic M-5 receptors, in the submandibular gland. However, muscarinic M, receptors may induce indirect effects via nitric oxide in the submandibular gland. (C) 2002 Elsevier Science B.V. All rights reserved.