title: GABAA- and glycine-mediated inhibitory modulation of the cough reflex in the caudal nucleus tractus solitarii of the rabbit.
abstract: Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Elenia
authors.initials: E
authors.lastname: Cinelli
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Iovino
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bongianni
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Florence, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Pantaleo
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Florence, Italy donatella.mutolo@unifi.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Mutolo
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003371:Cough / Q000503:physiopathology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000502:physiology; D018009:Receptors, Glycine / Q000502:physiology; D012018:Reflex; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology*; D013331:Strychnine / Q000494:pharmacology
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D009118:Muscimol; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline
keywords: GABAA receptors; control of breathing; cough reflex; glycine receptors; nucleus tractus solitarii