title: Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit.
abstract: We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (Tt). At the higher concentrations (5 mM and 1 mM, respectively), both drugs abolished the cough reflex. DAMGO and baclofen also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased Tt, owing to increases in expiratory time. The neurokinin-1 (NK(1)) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK(2) receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.
authors.affiliation: Dipartimento di Scienze Fisiologiche, Viale G. B. Morgagni 63, 50134 Florence, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Mutolo
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bongianni
authors.forename: Elenia
authors.initials: E
authors.lastname: Cinelli
authors.forename: Tito
authors.initials: T
authors.lastname: Pantaleo
mesh_terms: D000009:Abdominal Muscles / Q000294:innervation*; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage*; D001418:Baclofen / Q000008:administration & dosage; D003371:Cough / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003964:Diaphragm / Q000294:innervation*; D004576:Electromyography; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008845:Microinjections; D015288:Neurokinin A / Q000008:administration & dosage / Q000031:analogs & derivatives; D010446:Peptide Fragments / Q000008:administration & dosage; D010791:Phrenic Nerve / Q000187:drug effects* / Q000503:physiopathology; D010812:Physical Stimulation; D010880:Piperidines / Q000008:administration & dosage; D011817:Rabbits; D012018:Reflex / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects* / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000996:Antitussive Agents; D010446:Peptide Fragments; D010880:Piperidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D015288:Neurokinin A; D001418:Baclofen