Drooling Over Purinergic Receptors

Science Signaling  24 Feb 2009:
Vol. 2, Issue 59, pp. ec77
DOI: 10.1126/scisignal.259ec77

The binding of norepinephrine or acetylcholine to their receptors on acinar cells in salivary glands causes Ca2+ influx and stimulates fluid secretion. Nakamoto et al. now show that purinergic receptors can also trigger salivation. In ex vivo preparations of mouse submandibular glands (SMGs), fluid secretion was robustly elicited by adenosine triphosphate (ATP) when extracellular Ca2+ was available but was weakly elicited with uridine triphosphate (UTP), implicating the P2X family of purinergic receptors, which are insensitive to UTP and mediate Ca2+ influx from the extracellular environment upon ligand binding. To differentiate between P2X4 and P2X7­­ purinergic receptors in salivary glands, the authors used benzoyl-ATP (BzATP), a selective activator of P2X7 receptors. BzATP caused sustained saliva secretion in SMGs from wild-type mice but failed to evoke inward cation currents in acinar cells isolated from the SMGs of P2X7 null mice. Furthermore, ex vivo salivary rates and intracellular Ca2+ signaling in response to ATP were diminished in SMGs from P2X7 null mice compared with those from wild-type mice. Fluid secretion in SMGs from wild-type mice treated with the muscarinic agonist carbachol was partially inhibited when ATP was also present, leading the authors to speculate that ATP activation of the P2X7 receptor may regulate salivary gland responses to cholinergic stimulation.

T. Nakamoto, D. A. Brown, M. A. Catalán, M. Gonzalez-Begne, V. G. Romanenko, J. E. Melvin, Purinergic P2X7 receptors mediate ATP-induced saliva secretion by the mouse submandibular gland. J. Biol. Chem. 284, 4815–4822 (2009). [Abstract] [Full Text]