Sensory nerve- and neuropeptide-mediated relaxation responses in airways of Sprague-Dawley rats.
We examined the role of sensory nerves in mediating nonadrenergic inhibitory responses in airway segments isolated from male Sprague-Dawley rats. In the presence of adrenergic blockade, capsaicin (Cap; 1 microM) elicited marked relaxation responses in isolated bronchi precontracted with bethanechol (Beth). Cap-induced inhibitory responses were unaffected by tetrodotoxin (TTX), were attenuated by incubation of the airway with indomethacin (Indo), phosphoramidon, or RP-67580, but were abolished by previous exposure of the airway to Cap and by denuding the epithelium. Substance P (SP; 1 microM), neurokinins A and B (1 microM), and calcitonin gene-related peptide (0.1 microM) relaxed Beth-contracted airway segments to a similar extent. The SP-induced responses were unaffected by adrenergic blockade or by pretreatment with either TTX, phosphoramidon, or Cap, but were attenuated by RP-67580 and abolished by Indo and by denuding the epithelium. In anesthetized mechanically ventilated rats, Cap (50 and 100 micrograms/kg i.v.) elicited a dose-dependent reversal of the increase in lung resistance induced by an infusion of Beth. The Cap-induced bronchodilation was unaffected by pretreatment with propranolol alone or in combination with hexamethonium. SP (44 nmol/kg iv) also evoked bronchodilatory responses in intact animals, which were unaffected by propranolol and hexamethonium but were abolished by treatment of the animals with Indo. Electrical-field stimulation (EFS) evoked nonadrenergic noncholinergic relaxation responses in contracted airway segments. These EFS-induced inhibitory responses were markedly attenuated by treatment of the airway segment with TTX, Cap, or RP-67580. We conclude that neuropeptides released from Cap-sensitive sensory nerves have potent inhibitory effects in rat airways that are mediated, in part, by activation of neurokonin NK1 receptors on epithelium and subsequent release of an inhibitory prostaglandin(s).
Szarek
J L
JL
Marshall University School of Medicine, Department of Pharmacology, Huntington, West Virginia 25704-9388, USA.
Stewart
N L
NL
Spurlock
B
B
Schneider
C
C
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015288:Neurokinin A / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D001993:Bronchodilator Agents; D009479:Neuropeptides; D018723:Bethanechol; D013373:Substance P; D013779:Tetrodotoxin; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin