Abstract

Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells. [ 125I]DOI (±)-l-(2,5- dimethoxy-4-[ 125 I] iodophenyl)-2- aminopropane) , a 5-HT 2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT 2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT 1 and 5-HT 3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT 2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT 1A and 5-HT 1c receptors were not detectable. Moreover, RT-PCR indicated that 5-HT 2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT 2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC 50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT 2 receptor-mediated response. In addition, a number of selective 5-HT 2 receptor agonists (quipazine, α-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT 1 and 5-HT 3 receptor subtypes had little effect. These results indicate that the ability of serotonin to induce collagenase in the uterine smooth muscle cells is mediated by the 5-HT 2 receptor subtype, and that this receptor may be the only serotonin receptor subtype in this peripheral cell.

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