Salivary gland P2 nucleotide receptors.
The effects of ATP on salivary glands have been recognized since 1982. Functional and pharmacological studies of the P2 nucleotide receptors that mediate the effects of ATP and other extracellular nucleotides have been supported by the cloning of receptor cDNAs, by the expression of the receptor proteins, and by the identification in salivary gland cells of multiple P2 receptor subtypes. Currently, there is evidence obtained from pharmacological and molecular biology approaches for the expression in salivary gland of two P2X ligand-gated ion channels, P2Z/P2X7 and P2X4, and two P2Y G protein-coupled receptors, P2Y1 and P2Y2. Activation of each of these receptor subtypes increases intracellular Ca2+, a second messenger with a key role in the regulation of salivary gland secretion. Through Ca2+ regulation and other mechanisms, P2 receptors appear to regulate salivary cell volume, ion and protein secretion, and increased permeability to small molecules that may be involved in cytotoxicity. Some localization of the various salivary P2 receptor subtypes to specific cells and membrane subdomains has been reported, along with evidence for the co-expression of multiple P2 receptor subtypes within specific salivary acinar or duct cells. However, additional studies in vivo and with intact organ preparations are required to define clearly the roles the various P2 receptor subtypes play in salivary gland physiology and pathology. Opportunities for eventual utilization of these receptors as pharmacotherapeutic targets in diseases involving salivary gland dysfunction appear promising.
Turner
J T
JT
Department of Pharmacology, University of Missouri-Columbia School of Medicine, 65212, USA.
Landon
L A
LA
Gibbons
S J
SJ
Talamo
B R
BR
D000255:Adenosine Triphosphate / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology; D008967:Molecular Biology; D010539:Permeability; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018987:Salivary Ducts / Q000166:cytology; D012466:Salivary Gland Diseases / Q000188:drug therapy; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012471:Salivary Proteins and Peptides / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology
D007473:Ion Channels; D018048:Receptors, Purinergic P2; D012471:Salivary Proteins and Peptides; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D002118:Calcium