Purinergic P2X(7) Receptors Mediate ATP-induced Saliva Secretion by the Mouse Submandibular Gland

Nakamoto, Tetsuji; Brown, David A.; Catalan, Marcelo A.; Gonzalez-Begne, Mireya; Romanenko, Victor G.; Melvin, James E.

Abstract

Salivary glands express multiple isoforms of P2X and P2Y nucleotide receptors, but their in vivo physiological roles are unclear. P2 receptor agonists induced salivation in an ex vivo submandibular gland preparation. The nucleotide selectivity sequence of the secretion response was BzATP >> ATP > ADP >> UTP, and removal of external Ca2+ dramatically suppressed the initial ATP-induced fluid secretion (similar to 85%). Together, these results suggested that P2X receptors are the major purinergic receptor subfamily involved in the fluid secretion process. Mice with targeted disruption of the P2X(7) gene were used to evaluate the role of the P2X(7) receptor in nucleotideevoked fluid secretion. P2X(7) receptor protein and BzATPactivated inward cation currents were absent, and importantly, purinergic receptor agonist-stimulated salivation was suppressed by more than 70% in submandibular glands from P2X(7)-null mice. Consistent with these observations, the ATP-induced increases in [Ca2+](i) were nearly abolished in P2X(7)(-/-)submandibular acinar and duct cells. ATP appeared to also act through the P2X(7) receptor to inhibit muscarinic-induced fluid secretion. These results demonstrate that the ATP-sensitive P2X(7) receptor regulates fluid secretion in the mouse submandibular gland.

Más información

Título según WOS: ID WOS:000263416600009 Not found in local WOS DB
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 284
Número: 8
Editorial: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Fecha de publicación: 2009
Página de inicio: 4815
Página final: 4822
DOI:

10.1074/jbc.M808597200

Notas: ISI