Characterization of oxytocin receptors and serotonin transporters in mast cells.
Oxytocin (OT) inhibits the uptake of serotonin (5HT) into uterine mast cells. This may modulate 5HT bioavailability in the myometrium. Because 5HT isan important endogenous uterotonic compound, it has been postulated that this effect of OT may contribute to its potency as a labor inducer. This also predicts the presence of oxytocin receptors (OTRs) and transducing signals that will interact with 5HT transporters (SERT) in mast cells. In this study, OTR and SERT were characterized in murine peritoneal mast cells by radioligand-binding studies. Saturation assays for OTR showed no changes in Kd along the estrous cycle (6.95 +/- 2.76 nM in estrus and 4.07 +/- 1.73 nM in diestrus) but an increase in Bmax in estrus (0.71 +/- 0.08 pmol/10(6) cells and 0.37 +/- 0.05 pmol/10(6) cells in estrus and diestrus, respectively). Bmax and Kd for SERT were not affected along the estrous cycle. The signaling between the OTR and the SERT was analyzed by measuring the extent of inhibition of OT and PMA (activator of protein kinase C on 5HT uptake and the capability of Ro318220 (specific inhibitor of PKC) to increase 5HT uptake and block the effect of the above compounds in mast cells. The results showed that in murine peritoneal mast cells in vitro (1) ovarian hormones modulate OTR but not SERT expression, (2) the magnitude of OT action on 5HT uptake depends on the number of OTRs expressed in mast cells, and (3) the signaling between OTR and the SERT is mediated through the activation of protein kinase C. It is concluded that the ovarian hormones have a modulatory action on 5HT uptake which involves OT-mediated mechanism.
Vega
Edgardo
E
Department of Pharmacology, Facultad de Ciencias Biológicas, Universidad de Concepción, Chile.
Rudolph
Maria Isolde
MI
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D008407:Mast Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D011493:Protein Kinase C / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012701:Serotonin / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018045:Receptors, Oxytocin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014316:Tritium; D012701:Serotonin; D010121:Oxytocin; D011493:Protein Kinase C