Synthetic FP-prostaglandin-induced contraction of rat uterus smooth muscle in vitro.
Numerous synthetic FP-class prostaglandin (PG) analogs stimulated the contraction of isolated non-pregnant female rat uterus in a concentration-dependent manner with the following agonist potencies: bimatoprost acid (17-phenyl-trinor PGF(2alpha); EC(50)=0.68+/-0.06 nM)=cloprostenol (EC(50)=0.73+/-0.01 nM)>travoprost acid (EC(50)=1.3+/-0.07 nM)>latanoprost acid (EC(50)=2.7+/-0.08 nM)>PGF(2alpha) (EC(50)=52+/-11 nM)>unoprostone (UF-021; EC(50)=310+/-101 nM)>S-1033 (EC(50)=610+/-4 nM)>bimatoprost (EC(50)=1130+/-173 nM). The FP-receptor antagonist, AL-8810, antagonized the contractile effects of PGF(2alpha) (K(i)=2.9+/-0.2 microM), travoprost acid (K(i)=0.6+/-0.1 microM) and bimatoprost (K(i)=0.2+/-0.02 microM). Agonist and antagonist potencies for rat uterus contraction by these PGs compared well with their potencies for inducing/blocking functional responses in other systems (r=0.83-0.94) except with bovine iris sphincter (r=0.2; p<0.7). In conclusion, the rat uterus contains functionally active FP-receptors whose activation by a variety of free acid and an amide forms of synthetic PGs leads to the contraction of this tissue and which can be pharmacologically blocked by an FP-receptor antagonist, AL-8810.
Sharif
Najam A
NA
Alcon Research, Ltd., Fort Worth, TX 76134-2099, USA. naj.sharif@alconlabs.com
D000577:Amides / Q000494:pharmacology; D000818:Animals; D000069580:Bimatoprost; D002417:Cattle; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D000069557:Travoprost; D014590:Uterine Contraction
C507874:3-(3,5-dihydroxy-2-(oxodecyl)cyclopentyl)propionic acid; D000577:Amides; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; C121227:AL 8810; D003008:Cloprostenol; D015237:Dinoprost; D000069580:Bimatoprost; D000069557:Travoprost