Effects of McN‐A‐343 and DMPP on the uptake and release of ³H‐noradrenaline by guinea‐pig atria

Abstract

, responses of atria to noradrenaline were increased and those to tyramine were decreased. 5. DMPP had positive inotropic and chronotropic actions on atria, and these effects were accompanied by an increase in efflux of radioactivity from atria previously incubated with (-)-3H-noradrenaline.

ATROPINE‐RESISTANT EFFECTS OF THE MUSCARINIC AGONISTS McN‐A‐343 AND AHR 602 ON CARDIAC PERFORMANCE AND THE RELEASE OF NORADRENALINE FROM SYMPATHETIC NERVES OF THE PERFUSED RABBIT HEART

“…This is a potentially important site of blockade, in view of the recent suggestion that nicotinic drugs require to be transported intraneuronally by the noradrenaline uptake mechanism, as a prerequisite to effecting transmitter release (Su & Bevan, 1970;Bevan & Su, 1972;Allen et al, 1972). If such a mechanism were operating for DMPP in the rabbit heart, then it could be argued that cocaine, McN-A-343 and AHR 602 were inhibiting its effect by blocking its intraneuronal access.…”

EFFECTS OF THE MUSCARINIC AGONIST McN‐A‐343 ON THE RELEASE BY SYMPATHETIC NERVE STIMULATION OF [3H]‐NORADRENALINE FROM RABBIT ISOLATED EAR ARTERIES AND GUINEA‐PIG ATRIA

“…Although McN-A-343 inhibits noradrenaline uptake in the atria, 10-5 M producing about 50% inhibition (Allen et al, 1972), this concentration had no effect on the responses of the artery to injections of noradrenaline (Rand & Varma, 1971). …”

“…Recently it was shown that McN-A-343 is a potent inhibitor of [3 HI -noradrenaline uptake by guinea-pig atria, and that this action was atropine-insensitive (Allen, Rand & Story, 1972 …”

Comparison of effects of six cholinomimetic drugs on inhibition of uptake of 3H‐(±)‐noradrenaline by guinea‐pig atria

“…-Two cholinomimetic drugs, DMPP (N,N-dimethyl-N'-phenylpiperazinium) and McN-A-343 (4-(mchlorophenylcarbamoyloxy) -2 -butynyltrimethylammonium) are potent inhibitors of the uptake of noradrenaline by guineapig atria (Allen, Rand & Story, 1972). In isolated artery preparations, these drugs can cause increases or decreases in responses to sympathetic nerve stimulation, the particular effect depending on the frequency of stimulation and the concentration of drug (Malik & Ling, 1969a;Rand & Varma, 1971).…”

“…Methods.-The uptake of 3H-( + )-noradrenaline by guinea-pig atria and the effects of drugs on the uptake were measured as described by Allen et al (1972). Atria were incubated with 3H-(+)-noradrenaline (13 X 1O-7M, 05 ,uCi/ml) in Krebs-Henseleit solution at 370 C for 20 minutes.…”