Antagonism of cholinergic nerve-mediated contractions by the sensory nerve inhibitory system in rat bronchi.
The purpose of this study was to examine the potential functional significance of the sensory nerve inhibitory system in modulating contraction. Tension development in response to electrical field stimulation (EFS) and exogenous acetylcholine was monitored in segments of intrapulmonary bronchi isolated from male Sprague-Dawley rats. Contractile responses to EFS were enhanced by desensitization of sensory nerves with capsaicin, by antagonizing neurokinin NK1 receptors with RP-67580, and by inhibition of cyclooxygenase with meclofenamate. Except for RP-67580, which had a slight inhibitory effect on acetylcholine-induced contractions, these interventions were without effect on contraction to acetylcholine. Incubation of capsaicin-desensitized airway segments with substance P attenuated contractions evoked by a half-maximal frequency of EFS by approximately 92%, whereas contractions elicited by a half-maximal concentration of acetylcholine were not affected. Contractile responses elicited by a lower concentration of acetylcholine were inhibited by approximately 50% by substance P. The inhibitory effect of substance P was blocked by RP-67580, meclofenamate, and epithelial denudation. We conclude that the sensory nerve inhibitory system modulates cholinergic contractions and thus plays a role in the regulation of airway smooth muscle tone.
Szarek
J L
JL
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25704-9388, USA. SZAREK@MUSOM01.MU.WVNET.EDU
Spurlock
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004848:Epithelium / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology
D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D011453:Prostaglandins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D008469:Meclofenamic Acid; D000109:Acetylcholine; D002211:Capsaicin