title: Cyclic-AMP regulates postnatal development of neural and behavioral responses to NaCl in rats.
abstract: During postnatal development rats demonstrate an age-dependent increase in NaCl chorda tympani (CT) responses and the number of functional apical amiloride-sensitive epithelial Na+ channels (ENaCs) in salt sensing fungiform (FF) taste receptor cells (TRCs). Currently, the intracellular signals that regulate the postnatal development of salt taste have not been identified. We investigated the effect of cAMP, a downstream signal for arginine vasopressin (AVP) action, on the postnatal development of NaCl responses in 19-23 day old rats. ENaC-dependent NaCl CT responses were monitored after lingual application of 8-chlorophenylthio-cAMP (8-CPT-cAMP) under open-circuit conditions and under ±60 mV lingual voltage clamp. Behavioral responses were tested using 2 bottle/24h NaCl preference tests. The effect of [deamino-Cys1, D-Arg8]-vasopressin (dDAVP, a specific V2R agonist) was investigated on ENaC subunit trafficking in rat FF TRCs and on cAMP generation in cultured adult human FF taste cells (HBO cells). Our results show that in 19-23 day old rats, the ENaC-dependent maximum NaCl CT response was a saturating sigmoidal function of 8-CPT-cAMP concentration. 8-CPT-cAMP increased the voltage-sensitivity of the NaCl CT response and the apical Na+ response conductance. Intravenous injections of dDAVP increased ENaC expression and γ-ENaC trafficking from cytosolic compartment to the apical compartment in rat FF TRCs. In HBO cells dDAVP increased intracellular cAMP and cAMP increased trafficking of γ- and δ-ENaC from cytosolic compartment to the apical compartment 10 min post-cAMP treatment. Control 19-23 day old rats were indifferent to NaCl, but showed clear preference for appetitive NaCl concentrations after 8-CPT-cAMP treatment. Relative to adult rats, 14 day old rats demonstrated significantly less V2R antibody binding in circumvallate TRCs. We conclude that an age-dependent increase in V2R expression produces an AVP-induced incremental increase in cAMP that modulates the postnatal increase in TRC ENaC and the neural and behavioral responses to NaCl.
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Shobha
authors.initials: S
authors.lastname: Mummalaneni
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Tam-Hao T
authors.initials: TT
authors.lastname: Phan
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Gerard L
authors.initials: GL
authors.lastname: Heck
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: DeSimone
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: West
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Deanna
authors.initials: D
authors.lastname: Hojati
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.affiliation: Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Korea.
authors.forename: Mee-Ra
authors.initials: MR
authors.lastname: Rhyu
authors.affiliation: NYU College of Dentistry, New York, NY, United States of America.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Spielman
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mehmet Hakan
authors.initials: MH
authors.lastname: Özdener
authors.affiliation: Departments of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Vijay
authors.identifier: http://orcid.org/0000-0001-6567-5023
authors.initials: V
authors.lastname: Lyall
mesh_terms: D000328:Adult; D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002814:Chorda Tympani Nerve / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects* / Q000502:physiology; D013650:Taste Buds / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013873:Thionucleotides / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053503:Epithelial Sodium Channels; D017483:Receptors, Vasopressin; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D012965:Sodium Chloride; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin