title: Smooth muscle pharmacology in the isolated virgin and pregnant rat uterus and cervix.
abstract: Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle α-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 ± 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2α, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The β-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ∼10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ∼20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during pregnancy.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Darios
authors.forename: Bridget
authors.initials: B
authors.lastname: Seitz
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000199:Actins / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011460:Prostaglandins F / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D014590:Uterine Contraction / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D000318:Adrenergic beta-Agonists; D018679:Cholinergic Agonists; D011460:Prostaglandins F; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D009569:Nitric Oxide; D012701:Serotonin; D010121:Oxytocin; D002217:Carbachol; D007545:Isoproterenol