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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 77/6/960    most recent biolreprod.107.062562v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schuh, S. M Articles by Babcock, D. F Search for Related Content PubMed PubMed Citation Articles by Schuh, S. M Articles by Babcock, D. F Agricola Articles by Schuh, S. M Articles by Babcock, D. F

Adenosine and Catecholamine Agonists Speed the Flagellar Beat of Mammalian Sperm by a Non-Receptor-Mediated Mechanism¹

Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195

ABSTRACT

Activation of rapid motility apparently is one of the first steps of sperm capacitation and can be studied in vitro. Previously we found that 2-chloro-2'-deoxyadenosine or the catecholamine isoproterenol activates mouse sperm motility in vitro via a pathway mediated by cAMP that requires extracellular Ca²⁺, the atypical sperm adenylyl cyclase, and sperm-specific protein kinase A. We now show that several other adenosine analogs and catecholamines accelerate the flagellar beat of mouse and human sperm. Unexpectedly, the potent adenosine receptor agonist CGS21680 does not accelerate the beat, and the adenosine receptor antagonist DPCPX does not diminish the accelerating action of 2-chloro-2'-deoxyadenosine. The pharmacological profile for activation by catecholamines is also unusual. Both agonists and antagonists of beta-adrenergic receptors elevate the beat frequency. Moreover, both l-(–) and d-(+) isomers of epinephrine, norepinephrine, and isoproterenol produce similar acceleration of the beat. In contrast, inhibitors of equilibrative nucleoside transporters effectively slow the onset of the accelerating action of adenosine analogs. Replacement of external Na⁺ with Li⁺ also diminishes the accumulation of cAMP and slows the resultant accelerating action of 2-chloro-2'-deoxyadenosine, suggesting the involvement of a Na⁺-dependent concentrative nucleoside transporter. Our results show that adenosine and catecholamine agonists act in a novel signaling pathway that does not involve G protein-coupled cell-surface receptors that link to conventional adenylyl cyclases. Instead, adenosine and analogs may be transported into sperm via equilibrative and concentrative nucleoside transporters to act on unknown intracellular targets.

adenosine, cAMP, catecholamines, CNT, ENT, flagellar beat, nucleoside transporter, sAC, SLC28A, SLC29A, soluble adenylyl cyclase, sperm capacitation, sperm motility and transport

¹Supported by National Institute of Child Health & Human Development/National Institutes of Health (NIH) through cooperative agreement [U54 (HD12629)] as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. S.M.S. was supported in part by NIH grant 5T32 HD07183.

Correspondence: ²Donner F. Babcock, Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, WA 98195-7290. FAX: 206 685 3191; e-mail: donner{at}u.washington.edu