Electrophysiological effects of tachykinins and capsaicin on guinea-pig bronchial parasympathetic ganglion neurones.
1. We evaluated the effects of neurokinins, tachykinin analogues, or capsaicin on passive membrane properties of guinea-pig bronchial parasympathetic neurones using intracellular recording techniques. 2. Substance P (SP) and the tachykinin analogue, acetyl-[Arg6,Sar9,Met(O2)11]-SP(6-11) (ASMSP), at concentrations selective for the neurokinin (NK)-1 receptor subtype, depolarized the resting potential (3 and 5 mV, respectively) with no change in input resistance. Neurokinin A and beta Ala8NKA(4-10), at concentrations selective for the NK-2 receptor subtype (0.1 microM), were without effect. 3. Neurokinin B (NKB) and [Asp5,6,methyl-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%, respectively). 4. Capsaicin (1 microM) elicited a 3-24 mV depolarization of the resting potential of thirteen of eighteen bronchial ganglion neurones and decreased the input resistance of seven of thirteen of these neurones. The effects of capsaicin were reduced by desensitization with senktide analogue at a concentration selective for the NK-3 receptor subtype, whereas a non-peptide NK-1 receptor antagonist had no effect. 5. Using 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 estimated to be + 4 mV. 6. These data support the hypothesis that neurokinin-containing nerve terminals are localized within guinea-pig bronchial parasympathetic ganglia and, when released, the predominant effect of the neurokinins is by activation of NK-3 receptors.
Myers
A C
AC
Johns Hopkins Asthma and Allergy Center, Baltimore, MD.
Undem
B J
BJ
D000818:Animals; D001980:Bronchi / Q000294:innervation; D002211:Capsaicin / Q000494:pharmacology*; D004594:Electrophysiology; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D002211:Capsaicin