Effect of Noradrenaline on the Action of Nicotine and Tyramine on Isolated Atria

Abstract

Both nicotine (in the presence of atropine) and tyramine cause a rise in the rate of isolated rabbit atria. When noradrenaline is allowed to act on the atria for 20 to 30 min and then removed from the bath by repeated changes of the bath fluid, the action of nicotine and of tyramine is greatly increased. The first addition of noradrenaline to the bath often has a much smaller effect on the response to nicotine or to tyramine than have later additions. Sometimes the greater effect after the addition of nicotine persists for 2 or 3 hr. When reserpine is added to the bath and left in contact with the atria for 1 to 2 hr, and is then removed from the bath, the effect of noradrenaline on the atrial rate is much reduced in size and duration. Bretylium abolishes the action of nicotine but increases the action of tyramine.

Mechanism of Action of Guanethidine

“…Day & Rand (1961) showed that guanethidine inhibited the action of nicotine, but intensified the inhibitory effect of noradrenaline and adrenaline in the rabbit ileum. Reserpine added to the bath decreases the action of noradrenaline on isolated atria, and, as was suggested by Azarnoff & Burn (1961), this effect is connected with the inhibition of the uptake of noradrenaline, which was described by Muscholl (1960). Cass & Spriggs (1961) …”

“…It was concluded by Burn & Rand (1958a, b), Azarnoff & Burn (1961) and Burn (1961) that the presence of a catechol amine store was essential for the action of nicotine, tyramine and other amines. When this store was depleted by pretreatment with reserpine or by sympathetic degeneration (Burn & Rand, 1959) the action of these amines and of nicotine was blocked, while that of noradrenaline and adrenaline was potentiated.…”

“…Reserpine pretreatment inhibits the action of nicotine and tyramine on the isolated heart, heart papillary muscle and atria (Burn & Rand, 1958b;Bejrablaja, Burn & Walker, 1958 ; Leusen & Verbeke, 1960;Azarnoff & Burn, 1961). It was concluded by Burn & Rand (1958a, b), Azarnoff & Burn (1961) and Burn (1961) that the presence of a catechol amine store was essential for the action of nicotine, tyramine and other amines.…”

“…The method used here was based on that described by Azarnoff & Burn (1961). Freshly dissected rabbit atria were suspended in a 10 ml.…”

“…After 20 min the substances investigated were added to the bath and their action compared with that before the addition of guanethidine or reserpine. The action of noradrenaline and tyramine had never been investigated on the same preparation of atria, since, as was shown by Azarnoff & Burn (1961), the incubation of the atria with noradrenaline intensifies the action of tyramine and nicotine. As nicotine itself blocks the action of subsequent doses of nicotine, the normal response to nicotine was compared with that after prior incubation with guanethidine or reserpine in two different preparations of atria.…”