title: Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways.
abstract: The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ "cough receptors" such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Eric J
authors.identifier: 0000-0002-7706-311X
authors.initials: EJ
authors.lastname: Zaccone
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: TinaMarie
authors.initials: T
authors.lastname: Lieu
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Muroi
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Carl
authors.initials: C
authors.lastname: Potenzieri
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Blair E
authors.initials: BE
authors.lastname: Undem
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Peisong
authors.initials: P
authors.lastname: Gao
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Center of Sensory Biology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Canning
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
mesh_terms: D000818:Animals; D003371:Cough / Q000235:genetics / Q000276:immunology / Q000821:virology*; D015870:Gene Expression; D006168:Guinea Pigs; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology / Q000821:virology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009620:Nodose Ganglion / Q000276:immunology / Q000821:virology; D010224:Parainfluenza Virus 3, Human / Q000502:physiology*; D018184:Paramyxoviridae Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000821:virology; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000821:virology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000276:immunology / Q000294:innervation / Q000378:metabolism / Q000821:virology
chemical_list: D009414:Nerve Growth Factors; D050916:TRPV Cation Channels