Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.
1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.
Tobin
G
G
Department of Physiology and Pharmacology, Göteborg University, Sweden.
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013363:Submandibular Gland / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*
D018727:Muscarinic Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol