ELECTROPHYSIOLOGICAL EFFECTS OF TACHYKININS AND CAPSAICIN ON GUINEA-PIG BRONCHIAL PARASYMPATHETIC GANGLION NEURONS

1. We evaluated the effects of neurokinins, tachykinin analogues, or c apsaicin on passive membrane properties of guinea-pig bronchial parasy mpathetic neurones using intracellular recording techniques. 2. Substa nce P (SP) and the tachykinin analogue, acetyl-[Arg6,Sar9,Met(O2)11]-S P(6-11) (ASMSP), at concentrations selective for the neurokinin (NK)-1 receptor subtype, depolarized the resting potential (3 and 5 mV, resp ectively) with no change in input resistance. Neurokinin A and betaAla 8NKA(4-10), at concentrations selective for the NK-2 receptor subtype (0.1 mum), were without effect.3. Neurokinin B (NKB) and [Asp5,6, meth yl-Phe8]SP(5-11) (senktide analogue), at concentrations selective for NK-3 receptor subtype, elicited maximum depolarizations of 16 +/- 2 mV for both agonists. The peak of the depolarization was associated with an decrease in membrane resistance (35 +/- 4 and 50 +/- 7 % respectiv ely). 4. Capsaicin (1 mum) elicited a 3-24 mV depolarization of the re sting potential of thirteen of eighteen bronchial ganglion neurones an d decreased the input resistance of seven of thirteen of these neurone s. The effects of capsaicin were reduced by desensitization with senkt ide analogue at a concentration selective for the NK-3 receptor subtyp e, whereas a non-peptide NK-1 receptor antagonist had no effect. 5. Us ing voltage clamp analysis, capsaicin and senktide analogue evoked an inward current and an increase in membrane conductance at the resting membrane potential. The reversal potential for senktide analogue was e stimated to be + 4 mV. 6. These data support the hypothesis that neuro kinin-containing nerve terminals are localized within guinea-pig bronc hial parasympathetic ganglia and, when released, the predominant effec t of the neurokinins is by activation of NK-3 receptors.