Differential effects of ω‐conotoxin GVIA on cholinergic and non‐cholinergic secretomotor neurones in the guinea‐pig small intestine

Ussing chambers were used to study the effects of the specific N‐type Ca 2+ channel antagonist, ω‐conotoxin GVIA, on neurally evoked secretion across isolated submucosa/mucosa preparations from the small intestine of the guinea‐pig. Cholinergic and non‐cholinergic neurones were stimulated with 10 μ M dimethylphenylpiperazinium (DMPP). Non‐cholinergic secretomotor neurones were preferentially stimulated with 100 n M 5‐hydroxytryptamine (5‐HT), while cholinergic secretomotor neurones were preferentially stimulated with 3 μ M 5‐HT in the presence of the 5‐HT 2 receptor antagonist ketanserin (30 n M ). ω‐Conotoxin GVIA (1 n M –1 μ M ) depressed the secretion evoked by DMPP in a concentration‐dependent manner, but a substantial residual response was observed. Hyoscine (100 n M ) significantly depressed secretion evoked by DMPP, but did not prevent further depression of secretion by ω‐conotoxin GVIA. The toxin was substantially more effective when the non‐cholinergic secretomotor neurones were preferentially activated with 100 n M 5‐HT, with a decrease in the response of more than 75% of the control value in the presence of 1 μ M ω‐conotoxin GVIA. ω‐Conotoxin GVIA (1 μ M ) was relatively ineffective against secretion evoked by preferential activation of cholinergic secretomotor neurones with 3 μ M 5‐HT in the presence of 30 n M ketanserin, inhibiting the response by less than 33%. However, this inhibition was significant. Both 100 n M hyoscine and 300 n M tetrodotoxin abolished this effect of ω‐conotoxin GVIA. It is concluded that N‐type Ca 2+ channels play a major role in transmitter release from non‐cholinergic secretomotor neurones, but are not important for release from cholinergic secretomotor neurones in the guinea‐pig small intestine.British Journal of Pharmacology (1997) 121 , 232–236; doi: 10.1038/sj.bjp.0701071