Modulation of Purinoceptor mediated Ca2+ signals by β‐adrenergic receptor activation in Salivary Glands

Abstract

Crosstalk between Ca2+ signaling pathways has been demonstrated to facilitate secretory activity. However it is not known whether such a crosstalk exists between adrenergic receptor signaling pathway and a non‐cholinergic non‐adrenergic (NANC) pathway (purinergic pathway). In this study we use enzymatically isolated mouse parotid acini along with live cell Ca2+ imaging and pharmacological manipulations to assess crosstalk between these two pathways.We showed that [Ca2+]i rises induced by selective activation of P2X4R and P2X7R were potentiated three to eightfold following treatment with the cAMP elevating compounds forskolin, 8‐cpt‐cAMP or 3‐isobutyl‐1‐methylxanthine. Importantly, rises in cAMP levels evoked by β‐adrenergic receptor activation using isoprenalin also resulted in a marked enhancement of P2X‐mediated [Ca2+]i signals.Potentiation of P2X4R‐mediated [Ca2+]i signals following β‐adrenergic receptor activation was likely mediated by PKA because protein kinase inhibitor application in the presence of forskolin or isoprenalin abolished the enhancement of evoked [Ca2+]i signals. Interestingly, application of 2‐Aminoethoxydiphenyl borate during P2X7R stimulation also abolished the enhancement of [Ca2+]i rises following isoprenalin treatment.The results from this study reveal a crosstalk between purinergic and β‐adrenergic signaling pathways and may provide novel targets for construction of therapies for salivary hypofunction patients.