Promiscuous coupling and involvement of protein kinase C and extracellular signal-regulated kinase 1/2 in the adenosine A₁ receptor signalling in mammalian spermatozoa

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• 作者：Alba Minelli ; Ilaria Bellezza ; Giulia Collodel ; Bertil B. Fredholm
• 关键词：Protein G inhibitors ; Protein kinase inhibitors ; 2-Chloro-N⁶-cyclopentyladenosine ; [Ca²⁺]_i oscillations
• 刊名：Biochemical Pharmacology
• 出版年：2008
• 出版时间：15 February 2008
• 年：2008
• 卷：75
• 期：4
• 页码：931-941
• 全文大小：758 K

文摘

Mammalian spermatozoa require a maturational event after ejaculation that allows them to acquire the capacity for fertilisation. This process occurs spontaneously during the transit through the female reproductive tract where spermatozoa are in contact with micromolar concentrations of adenosine that might act as a capacitative effector. This study shows that the adenosine A₁ receptor agonist, 2-chloro-N⁶-cyclopentyladenosine, can induce capacitation, i.e., the ability to undergo the acrosome reaction and to become fertile. This receptor, already known to be bound to Gα_i2, is also bound to G_q/11. These G proteins are functional in the signalling pathway elicited by the A₁ receptor and correlate with the multiple intracellular events that follow its activation. The use of protein kinase C isoform inhibitors and MEK inhibitors, resulting in the abolition of the biological response to the selective agonist, indicates the involvement of protein kinase C and MEK in its signalling. In agonist-treated spermatozoa an extracellular calcium influx, involvement of α and γ PKC isoforms and transient phosphorylation of ERK1/2 have been observed. Our results, besides showing that adenosine A₁ receptor prompts mammalian spermatozoa to undergo the acrosome reaction hence supporting a role for adenosine as agent for fertilisation, show that 2-chloro-N⁶-cyclopentyladenosine triggers signalling mechanisms that involve both Gα_i2 and G_q/11, extracellular calcium influx, modulation of classical Ca²⁺-dependent PCK isoforms and up-regulation of the ERK1/2 phosphorylation.