Abstract
The ω-conotoxins GVIA, MVIIA, MVIIC and SVIB reduced in a concentration-dependent manner the low frequency electrically stimulated twitch response of the guinea pig ileum and rat vas deferens. The relative activities of the conotoxins showed some difference between the two preparations in that for ileum it was MVIIA=GVIA>MVIIC=SVIB and for the vas deferens it was MVIIA>GVIA≫SVIB>MVIIC. High frequency electrical stimulation of both preparations resulted in a neurally-mediated ω-conotoxin GVIA resistant component that was sensitive to high concentrations of either ω-conotoxin MVIIC (300 nM–1 μM) or ω-agatoxin IVA (300 nM–1 μM) but not to ω-conotoxin MVIIA. Lower levels of either ω-conotoxin MVIIC or ω-agatoxin IVA (30–100 nM) failed to significantly affect the ω-conotoxin GVIA resistant component. This ω-conotoxin GVIA resistant component was large in the ileal preparation comprising 30–40% of the maximal response at 20 Hz but relatively small (10%) in the vas deferens. These studies revealed that the N-type voltage-dependent calcium channel (VDCCs) exclusively controls neurotransmission during low frequency stimulation but at higher frequencies there is an additional non-adrenergic, non-cholinergic (NANC) neurotransmission that appears to be regulated via Q-type VDCC.
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