PROSTAGLANDINS EFFECTS OF EXPERIMENTAL DIABETES ON SPONTANEOUS CONTRACTIONS, ON THE OUTPUT OF PROSTAELANDINS AND ON THE METABOLISM OF LAEELLED ARACHIDONIC ACID, IN UTERI ISOLATED FROM OWARIECTOM Z D RATS. INFLUENCES OF ESTRADIOLtlt. A.M.Franchi(') M."ha'~12~;ld'~iE~::~~~~~2~~ M.A.F.'Eimeno . . I (2) Centro de Estudios Farmacolbgicos y de Principios Naturales (CEFAPRIN), Consejo National de Investigaciones Cientificas y Tbcnicas (CONICET). (3) Departamento de Farmacologia, Fa- cultad de Medicina, Universidad de Buenos Aires. ABSTRACT Spontaneous changes in isometric developed tension (IDT) as a function of time after isolation (contractile constancy) in uteri from control-castrated and castrated chronic streptozo- tocin-diabetic rats, were explored. The effects of injecting 17-beta estradiol (E,) were also studied. No differences in the minor changes of contractile constancy, between control and diabetic preparations, during a period of 60 min, were detected, whereas uteri from non-diabetic E, injected animals (0.5+1.0 ug, prior to sacrifice), exhibited a profound reduction of IDT, significantly greater than in tissues obtained from E, injected- diabetic rats. Moreover, basal generation and outputs into the suspending solution of prostaglandins (PEs) E,, E2 and FZd , were explored in the same groups, at 60 min following tissue isolation. The basal outputs of these three PEs were similar in castrated control rats, but preparations from castrated-dia- betics released significantly more PEE,. The administration of E, to castrated-diabetics, failed to alter the releases of the three PEs explored. In addition, the metabolism of labelled arachidonic acid (AA) into different prostanoids (Gketo-PEF, , PEFZ PEE and thromboxane BZ-TXBZ), was also investigated. The no;-dia etic 2 spayed rat uterus converted AA into these four prostanoids, the transformation into Gketo-PGFqoC(as an index of PEI2 formation) being the most prominent. In prepara- tions from diabetic rats the formation) being the most prominent. In preparations from diabetic rats the formation of b-keto- PBFq<, trols, PGF2<and PEE whereas a grea er % of TX82 formation (as an index of P' was significantly smaller than in con- TXA2), was detected. On the other hand uterine preparations from non-diabetic spayed rats injected with E. formed less 6- keto-PGFqOCand PEE:, and similar amounts of PEFZ<or of TX82 (1) Supported by Grant PID-3068000/85 from CONICET and by a Grant from Fundaci6n Albert0 J.Roemers. Mailing Address: Alvaro L. Eimeno, M.D. (CEFAPRIN) Serrano 665 (1414) Buenos Aires Argentina FEBRUARY 1988 VOL. 35 NO. 2 191