Abstract
A comparison was made of the ability of several pharmacological agents to alter the release of 3H-norepinephrine induced by nicotine with that of tyramine, potassium chloride and aminophylline. The following agents produced greater than 90% inhibition of nicotine-induced (9.2 x 10-5 M) release of 3H-norepinephrine: hexamethonium (1.8 x 10-5 M), morphine (3 x 10-4 M), cocaine (3.3 x 10-5 M) bretylium (10-5 M) and lidocaine (5 x 10-5 M). Cocaine and bretylium decreased the release by tyramine (3.1 x 10-4 M), but only lidocaine decreased the release induced by potassium chloride (6 x 10-2 M). None of these agents decreased the release of 3H-norepinephrine by aminophylline (5 x 10-3 M). Colchicine (1 mM) produced a significant decrease in the release by nicotine but not tyramine or potassium chloride. Prostaglandins E1 and E2 (10-6 M) decreased the release of 3H-norepinephrine by nicotine, potassium chloride and aminophylline but not tyramine. It is concluded that lidocaine blocks the nicotine-induced release of norepinephrine by a local anesthetic action on the adrenergic axonal membrane of the guinea-pig heart whereas hexamethonium acts by blocking the nicotinic receptor. Cocaine, bretylium and morphine are acting by blocking the nicotinic receptor or by acting at some latter step between receptor activation and norepinephrine release. Colchicine appears to be producing a specific anticholinergic effect in decreasing the release of norepinephrine. Prostaglandins E1 and E2 both decrease the release of norepinephrine at a step in secretion-coupling common to nerve stimulation and the administration of nicotine, potassium chloride and aminophylline.
Footnotes
- Received July 28, 1973.
- Accepted February 12, 1974.
- © 1974 by The Williams & Wilkins Co.
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