Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances
Article first published online: 26 MAY 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Volume 163, Issue 4, pages 745–754, June 2011
How to Cite
Dixon, R., Hwang, S., Britton, F., Sanders, K. and Ward, S. (2011), Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances. British Journal of Pharmacology, 163: 745–754. doi: 10.1111/j.1476-5381.2011.01266.x
- Issue published online: 26 MAY 2011
- Article first published online: 26 MAY 2011
- Received; 19 February 2010; Revised; 7 December 2010; Accepted; 13 December 2010
- female reproductive tract;
- smooth muscle;
BACKGROUND AND PURPOSE
Spontaneous electrical activity, termed slow waves, drives rhythmic, propulsive contractions in the smooth muscle of the oviduct (myosalpinx). Myosalpinx contractions cause egg transport through the oviduct. Agents that disrupt slow wave pacemaker activity will therefore disrupt myosalpinx contractions and egg transport. Caffeine is commonly used as a ryanodine receptor agonist and has been previously associated with delayed conception. Here we assessed the effects of caffeine on pacemaker activity in the murine myosalpinx.
The effects of caffeine on electrical pacemaker activity were studied using intracellular microelectrode and isometric force measurements on intact oviduct muscle preparations. Responses to caffeine were compared with responses caused by 3-isobutyl-1-methylxanthine (IBMX) and forskolin.
Caffeine caused hyperpolarization of membrane potential and inhibited slow wave generation and myosalpinx contractions. The effects of caffeine could be mimicked by the KATP channel agonist pinacidil and antagonized by the KATP channel antagonist glibenclamide. Caffeine is known to inhibit cyclic nucleotide phosphodiesterases (PDEs), leading to an increase in cytosolic cAMP and stimulation of downstream cAMP-dependent mechanisms. The effects of caffeine were mimicked by the PDE inhibitor, IBMX, and the adenylyl cyclase activator forskolin. These effects were also reversed by glibenclamide.
CONCLUSIONS AND IMPLICATIONS
These results suggest that caffeine activates KATP channels in oviduct myosalpinx. Since caffeine abolishes slow waves and associated contractions of the myosalpinx, it would have a negative effect on egg transport through the oviduct and may contribute to the documented delayed conception in women consuming caffeinated beverages.