Transduction mechanisms of P2Z purinoceptors.
The ability of extracellular ATP to increase the cation permeability of a variety of fresh and cultured cells has been known for decades, but evidence of a separate class of P2 purinoceptor, termed P2Z, which mediates this effect has only recently been obtained. Several features of the P2Z purinoceptor clearly distinguish it from other P2 purinoceptors and show that it is a ligand-gated ion channel. P2Z purinoceptors are highly selective for the ATP4- species and addition of Mg2+ in excess over ATP closes the channel. The most potent agonist is 3'-O-(4-benzoyl)benzoyl ATP which has a 10-fold lower EC50 than ATP. Ca2+ is the preferred permeant for the P2Z ion channel although it will pass ions up to the size of ethidium(+) (314 Da) in lymphocytes or fura-2 (813 Da) in macrophages. The inhibitors of the P2Z purinoceptor or its associated ion channel include suramin, amiloride analogues, high extracellular Na+ concentrations and 2',3'-dialdehyde ATP (oxidized ATP), which blocks irreversibly. Occupancy of P2Z purinoceptors stimulates a phospholipase D activity, which may be involved in membrane remodelling. Moreover, extracellular ATP causes loss of the glycosylated adhesion molecule L-selection from the surfaces of human lymphocytes by enzymic cleavage, suggesting a possible role for P2Z purinoceptors in intercellular interactions.
Wiley
J S
JS
Haematology Department, Austin Hospital, Heidelberg, Victoria, Australia.
Chen
J R
JR
Snook
M S
MS
Gargett
C E
CE
Jamieson
G P
GP
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology
D007473:Ion Channels; C546468:P2RX7 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D019041:L-Selectin; D000255:Adenosine Triphosphate; D012964:Sodium; D010739:Phospholipase D