Chemoreceptor responses to substance P, physalaemin and eledoisin: evidence for neurokinin-1 receptors in the cat carotid body.
Substance P (SP) belongs to a group of peptides called tachykinins. Biological effects of SP are mediated by tachykinin receptors that have been classified as neurokinin-1 (NK-1), NK-2 and NK-3 subtypes. The aim of the present study is to elucidate the tachykinin receptor subtype(s) that mediate the excitatory effects of SP in the carotid body. For this purpose, we compared the carotid body responses elicited by SP with that of physalaemin and eledoisin. In other tissues, physalaemin exhibits equi or greater potency at NK-1 receptors and eledoisin exerts its effects more on NK-2 and NK-3 subtypes compared to SP. Experiments were performed on eight cats that were anaesthetized, paralyzed and artificially ventilated with room air. Close carotid body administration of SP and physalaemin produced dose-dependent augmentation of the chemoreceptor afferent activity. Chemoreceptor discharge, however, was unaffected by eledoisin. Compared to that by SP, the magnitude of excitation produced by physalaemin was the same at lower doses but significantly greater with the highest dose (100 nmol). The time course of the response induced by physalaemin, however, was the same as that by SP. The present results demonstrate that in the carotid body physalaemin is also either equi or relatively more potent than SP, whereas eledoisin has no effect on the chemoreceptor discharge. It is suggested that stimulation of the carotid body by SP is mediated by NK-1 but not NK-2 or NK-3 receptors.
Prabhakar
N R
NR
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Kou YuR
Runold
M
M
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004600:Eledoisin / Q000494:pharmacology*; D005260:Female; D008297:Male; D015288:Neurokinin A / Q000502:physiology; D010803:Physalaemin / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D010803:Physalaemin; D013373:Substance P; D004600:Eledoisin; D015288:Neurokinin A