Ca2+ Signaling and P2 Receptors in Airway Smooth Muscle
Adenosine 5′-triphosphate (ATP) acts as an extracellular mediator with direct biological effects mediated by purinergic 2 (P2) receptors in different tissues, including the respiratory system. ATP is hydrolyzed by ectonucleotidases, enzymes bound to the plasma membrane. There are three major families of ATP-hydrolyzing ectonucleotidases: the ectonucleotide triphosphate diphosphohydrolases, the ectonucleotide pyrophosphatase/phosphodiesterases, and the alkaline phosphatases. ATP induces a biphasic response (a contraction followed by a relaxation) in airway smooth muscle of different species (guinea pig and rat), including human bronchial rings. In the majority of the species, ATP-induced contraction is associated to an increment of intracellular Ca2+ concentration ([Ca2+]i) mediated by stimulation of P2Y or P2X receptors in the airway smooth muscle. In the guinea-pig airway smooth muscle the contraction is mediated by bronchoconstrictor prostaglandins (thromboxane) and involves P2Y4 and P2Y6 receptors on the airway epithelium. However, epithelium removal prevents ATP-induced contraction and, paradoxically, induces relaxation without affecting the Ca2+ signaling. This ATP-induced relaxation occurs by smooth muscle prostaglandin production (PGE2), which involves a Gs protein activation and the subsequent enhancement of voltage-dependent K+ and Ca2+-dependent K+ channels. Activation of these K+ channels occurs through adenylyl cyclase-cAMP pathway. The physiological role of P2X and P2Y receptors in airway smooth muscle is complex and species dependent, and it would be expected to change during inflammation. Thus, further research is required in asthma to determine the purinoceptorsʼ role during this pathology.
KeywordsAirway smooth muscle ATP Purinergic receptors P2X receptors P2Y receptors
This study was partly supported by a grant from DGAPA-UNAM (IN200613-3) to Dr Luis M. Montaño.
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