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. Author manuscript; available in PMC: 2020 Sep 1.
Published in final edited form as: Andrology. 2019 May 1;7(5):631–643. doi: 10.1111/andr.12632

Figure 3). Model showing the coordinated interaction between PCs and CCs for the activation of V-ATPase-dependent proton secretion in CCs.

Figure 3)

Stimulation of PCs by basolateral factors such as adenosine, adrenergic agonists or neurotransmitters elevate intracellular cAMP, which in turns activates bicarbonate secretion via apical CFTR. Luminal bicarbonate then reaches CCs, where it activates the soluble adenylate cyclase (sAC) to produce cAMP. CFTR also stimulates ATP secretion via pannexin activation. ATP either activates P2X4 located on the apical membrane of CCs, or is hydrolyzed by extracellular ectonucleotidases to produce adenosine. Adenosine activates the GPCR receptor ADORA2B (A2B) located on the apical membrane of CCs, leading to elevation in intracellular cAMP. Activation of the cAMP/PKA pathway by bicarbonate or adenosine induces V-ATPase apical membrane accumulation. On the other hand, activation of P2X4 by luminal ATP in CCs induces an elevation of intracellular calcium, which also facilitates V-ATPase membrane accumulation. The redistribution of V-ATPase from intracellular vesicles to the apical membrane results in the formation and elongation of V-ATPase-enriched microplicae in CCs and stimulates proton secretion.