Agonist Discrimination between Uterine and Cervical Contractility

Smooth muscle is an important target in development of new treatments for premature labor. We hypothesized that an agonist existed that could discriminate between the uterus and cervix in stimulating smooth muscle function. The tissue bath was used to measure isometric contraction of uterine horns and cervices from virgin female Sprague‐Dawley rats. A majority of compounds tested contracted both uterus and cervix (maximum integrated area as % initial KCl contraction; uterus, cervix); oxytocin (53946±3607, 8121±870), carbamylcholine (42803±3057, 20219±1006) and ET‐1 (35451±3549, 10099±1448). However, substance‐P (1874±2741, N/A) and Ang1‐7 (5248±887, N/A) contracted the uterus to a greater magnitude than cervix. Relaxant agonists (% of half‐maximal oxytocin‐induced contraction remaining; uterus, cervix), norephinephrine (1.7±4.7, 27.0±5.1) and adenylate cyclase activator forskolin (15.1±5.3, −5.0±5.0) relaxed both tissues. However, sodium nitroprusside did not relax contracted tissues (89.1±9.0, 76.7±4.7). Only CGRP showed selectivity between tissues, relaxing the cervix (55.8±4.6, −4.3±15.8). We identified three agonists which produce relatively selective responses between uterine and cervical smooth muscle: Ang1‐7, substance‐P and CGRP. Extension of these studies in pregnant rats will determine whether tissue selectivity could help better control premature labor.