Relaxation of rat distal colon by activation of muscarinic, neuronal receptors: possible involvement of P(2y)-purinoceptors.

McN-A-343, which is a ligand at muscarinic receptors on myenteric ganglia, was found to concentration-dependently (1-44 microM) elicit non-adrenergic relaxation of the longitudinal muscle of rat distal colon, having been precontracted with carbachol (1 microM). This effect was partly antagonized by the muscarinic receptor antagonist, pirenzepine (0.3 microM), the nerve blocker, tetrodotoxin (1 microM), or by drugs which interfere with purinergic neurotransmission (apamin [0.5 microM], reactive blue 2 [50 microM]). Blockade of nitric oxide synthase (L-NNA [100 microM]), or of the cAMP (H-89 [1 microM]), or cGMP (ODQ [10 microM]) second messenger pathways did not affect the relaxatory response to McN-A-343 (14 microM). An additional, non-neurogenic component of the relaxation to this compound on carbachol induced tone is suggested to reflect a partial antagonism of the muscarinic receptors on the gut muscle by McN-A-343.