Further evidence for the involvement of Na+ channels in the release of adrenal catecholamine: the effect of scorpion venom and grayanotoxin I.

1 The effects of venom from the scorpion, Leiurus quinquestriatus, and grayanotoxin I on catecholamine secretion were studied in the perfused adrenal glands of guinea-pig. 2 Scorpion venom (0.1 to 10 micrograms/ml) caused a dose-dependent increase in catecholamine output. The response to the venom was partially inhibited by atropine (0.5 mM) plus hexamethonium (1mM). The dose-response curve was shifted to the right in the presence of these blocking agents. 3 Grayanotoxin I (0.1 to 0.5 mM) caused a dose-dependent increase in catecholamine output which was significantly reduced by atropine (0.5 mM) plus hexamethonium (1 mM). However, when grayanotoxin I (0.1 mM) was applied together with scorpion venom (0.1 micrograms/ml, a concentration which alone, was almost ineffective) the maximum catecholamine output was reached even in the presence of atropine plus hexamethonium. 4 Tetrodotoxin (0.1 or 0.2 microM) reversibly inhibited the secretory response induced by scorpion venom (10 micrograms/ml) and grayanotoxin I (0.1 mM) plus scorpion venom (0.1 micrograms/ml). 5 Scorpion venom and grayanotoxin I plus scorpion venus did not cause catecholamine secretion in the absence of extracellular Na+ or Ca2+ ions. However, the secretory response was restored by reintroduction of Na+ or Ca2+ ions. 6 It is suggested that both scorpion venom and grayanotoxin I activate Na+ channels on the chromaffin cell and result in catecholamine secretion.