In the longitudinal muscle-myenteric plexus preparation (LMMP) of the guinea-pig ileum, the non-opioid σ receptors agonists, 1,3-di-ortho-tolylguanidine (DTG) and (+)N-allyl-N-normetazocine [(+)SKF 10,047], had opposite effects on nerve-mediated cholinergic contractions caused by electrical field stimulation. DTG (0.1-10 μM) inhibited and (+)SKF 10,047 (0.1-10 μM) markedly enhanced these contractile responses. Both effects were evaluated in the presence (0.5 or 1 μM) of the putative antagonists at central σ sites: haloperidol, rimcazole, BMY 14802 and dextromethorphan. Haloperidol and dextromethorphan were ineffective. Rimcazole antagonized the effect of both DTG and (+)SKF 10.047. BMY 14802 antagonized the (+)SKF 10,047-mediated excitatory response only. These results suggest that two σ receptor subtypes are present in enteric cholinergic motor neurons innervating the longitudinal coat. Rimcazole and BMY 14802 may provide useful tools for the characterization of peripheral non-opioid σ receptors. © 1991.
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