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Intracellular cAMP and calcium signaling by serotonin in mouse cumulus-oocyte complexes Amireault P, et al .
Cyclic AMP (cAMP) and intracellular Ca(2+) are important second messengers involved in mammalian follicular growth and oocyte meiotic maturation. We investigated the capacity of the neurohormone serotonin(or 5-hydroxytryptamine, 5-HT) to regulate intracellular cAMP and Ca(2+) in mouse oocytes and surrounding cumulus cells. Based on a RT-PCR study, 5-HT7 receptor mRNA is expressed in cumulus cells, oocytes and embryos up to the 4 cell-stage and 5-HT2A and 5-HT2B receptor mRNAs in cumulus cells only, while 5-HT2C, 5-HT4 and 5-HT6 receptors are expressed neither in oocytes nor cumulus cells. The addition of 5-HT (10 nM-10 microM) to isolated metaphase II-oocytes had no effect on their internal cAMP or Ca(2+) levels whereas it caused dose-dependent cAMP and Ca(2+) increases in cumulus cells. This cAMP increase in cumulus cells could be mimicked by 5-HT agonists with the following order of potency: 5-HT > 8-OH DPAT = alpha-methyl 5-HT = 5-CT, thereby supporting a preferential involvement of 5-HT7 receptors. As measured with cumulus cells pre-loaded with fura2-AM, the addition of 5-HT also caused dose-dependent Ca(2+) rises, likely linked to detected 5-HT2A and 5-HT2B receptors. Adding the Ca(2+) ionophore ionomycin to cumulus cells resulted in both Ca(2+) and cAMP rises whereas preincubation of cells with the Ca(2+) chelator BAPTA-AM abolished the 5-HT induced Ca(2+) rise and reduced the cAMP increase, thus indicating a cross-talk between the 5-HT-sensitive Ca(2+) and cAMP pathways. Our results show that 5-HT may be a local regulator in mouse cumulus-oocyte complexes through its actions on cAMP and Ca(2+) signaling, as mediated by 5-HT2A, 5-HT2B and 5-HT7 receptors.
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