Extracellular cAMP elicits contraction of rat vas deferens: Involvement of ecto-5′-nucleotidase and adenosine A1 receptors

Autor(es)

Pacini, Enio Setsuo Arakaki ; Moro, Raissa de Paula ; Godinho, Rosely Oliveira

• Tipo de documento: Artigo Científico
• Fonte: Toxicology and Applied Pharmacology; v. 491, p. 9-pg., 2024-08-20.

Resumo

Aims: It is well established that intracellular cAMP contributes to the relaxation of vas deferens smooth muscle. In many tissues, intracellular cAMP is actively transported to the extracellular space, where it exerts regulatory functions, via its metabolite adenosine. These actions take place through the cAMP conversion to adenosine by ectoenzymes, a process called "extracellular cAMP-adenosine pathway". Herein, we investigated whether, in addition to ATP, extracellular cAMP might be an alternative source of adenosine, influencing the contraction of vas deferens smooth muscle. Main methods: The effects of cAMP, 8-Br-cAMP and adenosine were analyzed in the isometric contractions of rat vas deferens. cAMP efflux was analyzed by measuring extracellular cAMP levels after exposure of vas deferens segments to isoproterenol and forskolin in the presence or absence of MK-571, an inhibitor of MRP/ABCC transporters. Key findings: While 8-Br-cAMP, a cell-permeable cAMP analog, induced relaxation of KCl-precontracted vas deferens, the non-permeant cAMP increased the KCl-induced contractile response, which was mimicked by adenosine, but prevented by inhibitors of ecto-5 '-nucleotidase or A1 receptors. Our results also showed that isoproterenol and forskolin increases cAMP efflux via an MRP/ABCC transporter-dependent mechanism, since it is inhibited by MK-571. Significance: Our data show that activation of beta-adrenoceptors and adenylyl cyclase increases cAMP efflux from vas deferens tissue, which modulates the vas deferens contractile response via activation of adenosine A1 receptors. Assuming that inhibition of vas deferens contractility has been proposed as a strategy for male contraception, the extracellular cAMP-adenosine pathway emerges as a potential pharmacological target that should be considered in studies of male fertility. (AU)

• Processo FAPESP: 23/03689-1 - Impacto da via extracelular AMPc-adenosina na função sinalizadora do AMPc
• Beneficiário: Rosely Oliveira Godinho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/06627-0 - Participação da via extracelular AMPc-adenosina na contração de músculo liso vascular e não vascular
• Beneficiário: Raíssa de Paula Moro
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/21381-6 - Validação da "Via Extracelular AMPc-Adenosina" como novo alvo terapêutico para o tratamento de doenças respiratórias crônicas
• Beneficiário: Rosely Oliveira Godinho
• Modalidade de apoio: Auxílio à Pesquisa - Regular