EFFECTS OF NICOTINE, DIMETHYLPHENYLPIPERAZINIUM AND CHOLINERGIC BLOCKING AGENTS AT ADRENERGIC NERVE ENDINGS OF THE RABBIT PULMONARY ARTERY

¹ Department of Pharmacology, UCLA School of Medicine, Los Angeles, California

The contraction of the rabbit isolated pulmonary artery to postganglionic nerve stimulation was blocked by dimethyiphenyl-piperazinium (DMPP) but not by nicotine or the nicotine metabolite, cotinine. The DMPP-induced block was reversed by repeated washing of the preparation. The extent of the DMPP-induced block was the same whether the frequency of nerve stimulation was 5 or 25 pulses/sec. The neurogenic response of the artery was decreased slightly by (+)-tubo-curarine, potentiated slightly by mecamylamine and not altered by hexamethonium. Prior addition of either of these cholinergic blocking agents or nicotine did not prevent the blocking effect of DMPP. The contractile response of the artery to exogenous norepinephrine was either increased slightly or unaltered by DMPP, depending on the concentration of the latter, whereas nicotine was without any effect. The data demonstrate that DMPP and nicotine differ in their action on adrenergic nerve-smooth muscle transmission. The resuits support the view that DMPP is an adrenergic neuronal blocking agent which does not act on classical nicotinic receptors. The failure of nicotine to block adrenergic transmission in the pulmonary artery preparation contrasts with the blocking effect of this drug at other sites of sympathetic neuroeffector transmission. The absence of a blocking effect by either nicotine or mecamylamine cannot be explained in terms of the "cholinergic link" theory of Burn and Rand.