Evidence of mammalian Ca2+ channel inhibitors in venom of the spider Plectreurys tristis.

Plectreurys tristis venom inhibited K(+)-stimulated Ca2+ influx in a concentration-dependent manner in rat (0.5-4.0 micrograms venom protein/ml) and chicken (1.0-64.0 micrograms venom protein/ml) brain synaptosomes. In contrast to Hololena curta venom or omega conotoxin GVlA which both show selectivity for avian synaptosomes, inhibition of Ca2+ influx by the venom appeared to be relatively selective for rat synaptosomes. Plectreurys tristis venom also inhibited K(+)-evoked release of [3H](-)-noradrenaline from labeled rat cortical synaptosomes. Responses to electric field stimulation of the sympathetically innervated rat vas deferens in vitro were inhibited by Plectreurys tristis venom at dilutions similar to those which inhibited Ca2+ influx in synaptosomes. Inhibition persisted following washout of the venom. K(+)-evoked contractions of rat aortic rings were relaxed by the dihydropyridine antagonist (-)-202-791, but not by Plectreurys tristis venom, thus precluding an effect on K(+)-depolarized smooth muscle L-type channels. Contractions to exogenous (-)-noradrenaline in rat aorta were not inhibited by Plectreurys tristis venom, ruling out an effect on alpha 1-adrenergic receptors, and further suggesting a prejunctional site of action. The results suggest that this venom inhibits N-type Ca2+ channels, as well as unclassified Ca2+ channels, which are neither N- nor L-type.