pumiliotoxin-b and Arrhythmias--Cardiac

Semi-purified extracts of the skin of the Australian myobatrachid frog Pseudophryne coriacea (PS)displayed striking, reversible and, in part, dose-dependent effects on the systemic blood pressure of the rat and other experimental animals, as well as on the rat heart. The blood pressure response in the rat consisted typically in an abrupt, short-lasting fall, followed by a conspicuous, more persistent rise. The fall in pressure was abolished by atropine and potentiated by physostigmine, indicating a cholinergic mechanism; rise was abolished by prazosin and guanethidine, suggesting a release of catecholamines from adrenergic nerve terminals in the vasculature. Tachyphylaxis was the obvious result of exhaustion of stores of catecholamines. On the heart, as shown in the electrocardiographic tracings, PS produced a variety of rhythm disorders, attributable both to the release of aminergic transmitters and to a direct effect on the myocardium. Whereas the pressure and electrocardiographic responses were virtually unaffected by calcium channel antagonists and agonists, all the effects of PS were sharply reduced or completely abolished by the sodium channel blocker tetrodotoxin. This suggests that activation of sodium channels may play a role in the mechanism of action of PS. However, the exact nature of ionic flux(es)influenced by the extract of frog skin remains to be established.

Topics: Adrenalectomy; Alkaloids; Animals; Anura; Arrhythmias, Cardiac; Autonomic Agents; Blood Pressure; Calcium; Dogs; Electrocardiography; Guinea Pigs; Heart; In Vitro Techniques; Indolizines; Male; Oxygen Consumption; Piperidines; Rabbits; Rats; Rats, Inbred Strains; Salivation; Skin Physiological Phenomena; Sodium; Tissue Extracts