Signaling pathways for modulation of mouse sperm motility by adenosine and catecholamine agonists.
Capacitation of mammalian sperm, including alterations in flagellar motility, is presumably modulated by chemical signals encountered in the female reproductive tract. This work investigates signaling pathways for adenosine and catecholamine agonists that stimulate sperm kinetic activity. We show that 2-chloro-2'-deoxyadenosine and isoproterenol robustly accelerate flagellar beat frequency with EC50s near 10 and 0.05 microM, respectively. The several-fold acceleration is maximal by 60 sec. Although extracellular Ca2+ is required for agonist action on the flagellar beat, agonist treatment does not elevate sperm cytosolic [Ca2+] but does increase cAMP content. Acceleration does not require the conventional transmembrane adenylyl cyclase ADCY3, since it persists in sperm of ADCY3 knockout mice and in wild-type sperm in the presence of the inhibitors of conventional adenylyl cyclases SQ-22536, MDL-12330A, or 2', 5'-dideoxyadenosine. In contrast, the acceleration by these agents is absent in sperm that lack the predominant atypical adenylyl cyclase, SACY. Responses to these agonists are also absent in sperm from mice lacking the sperm-specific Calpha2 catalytic subunit of protein kinase A (PRKACA). Agonist responses also are strongly suppressed in wild-type sperm by the protein kinase inhibitor H-89. These results show that adenosine and catecholamine analogs activate sperm motility by mechanisms that require extracellular Ca2+, the atypical sperm adenylyl cyclase, cAMP, and protein kinase A.
Schuh
Sonya M
SM
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA.
Carlson
Anne E
AE
McKnight
G Stanley
GS
Conti
Marco
M
Hille
Bertil
B
Babcock
Donner F
DF
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000819:agonists*; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000819:agonists*; D000242:Cyclic AMP / Q000378:metabolism; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013081:Sperm Motility / Q000187:drug effects* / Q000502:physiology*; D013082:Sperm Tail / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
D002395:Catecholamines; D004791:Enzyme Inhibitors; D007097:Imines; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C017759:9-(tetrahydro-2-furyl)-adenine; D016048:Dideoxyadenosine; C014925:RMI 12330A; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517758:Prkaca protein, mouse; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3; D000225:Adenine; D000241:Adenosine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium