Atrial natriuretic factor intracellular signaling in the rat submandibular gland.
We previously reported that intravenously administered atrial natriuretic factor (ANF) induced no salivation but enhanced agonist-evoked secretion in submandibular glands. The gene expression of ANF and natriuretic peptide receptors (NPR) was later reported in the glands. In the present study we sought to establish the intracellular signalling mechanisms underlying ANF modulation of salivary secretion. Fasted rats were prepared with submandibular duct and femoral cannulation. Dose-response curves to methacholine (MC) and norepinephrine (NE) were performed in the presence of cANP (4-23 amide) (selective NPR-C agonist) and ANF. Local injection of the agonist or ANF-induced no salivation, but enhanced MC and NE-evoked secretion. ANF and cANP (4-23 amide) enhanced phosphoinositide turnover being the effect abolished by U73122 (PLC inhibitor). Further ANF and cANP (4-23 amide) decreased basal cAMP content but failed to affect isoproterenol or forskolin-evoked cAMP. ANF response was inhibited by pertussis toxin and mimicked by cANP (4-23 amide) strongly supporting NPR-C activation. ANF-induced cAMP reduction was abolished by PLC and PKC inhibitors. The content of cGMP was dose dependently stimulated by ANF but not modified by cANP (4-23 amide). These findings support that ANF through NPR-C receptors coupled to PLC activation and adenylyl cyclase inhibition interacts with sialogogic agonists in the submandibular gland to potentiate salivation.
Ventimiglia
María S
MS
Cátedras de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires Junin 956 Piso 5 (1113AAD) Buenos Aires, Argentina.
Rodríguez
Myrian R
MR
Elverdín
Juan C
JC
Davio
Carlos A
CA
Vatta
Marcelo S
MS
Bianciotti
Liliana G
LG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016210:Methacholine Chloride / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013363:Submandibular Gland / Q000378:metabolism / Q000502:physiology*
D016210:Methacholine Chloride; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D009638:Norepinephrine