Martha V. Oropeza

Anatomical differences in uterine sensitivity to prostaglandin F2α and serotonin in non-pregnant rats

The ovarian steroids regulate the sensitivity of a population of uterine receptors to prostaglandin F(2alpha), serotonin and oxytocin. However, the uterine sensitivity to prostaglandin F(2alpha) and oxytocin does not coincide with the estrogen-induced increase in the number of receptors. Anatomical differences affect the uterine sensitivity to agonists. We investigated whether anatomical differences between ovarian and cervical uterine regions modulate the hormone-regulated sensitivity to prostaglandin F(2alpha), serotonin and oxytocin. Non-cumulative concentration-response curves for these agonists were recorded for ovarian and cervical uterine segments from adult ovariectomized rats treated with 17beta-estradiol, 17beta-estradiol+progesterone, or vehicle. The ovarian segments displayed a higher maximal response (E(max)) to prostaglandin F(2alpha) and a lower E(max) to serotonin than the cervical segments. Both uterine segments displayed a similar sensitivity to oxytocin. The ovariectomized controls displayed the highest E(max) and the lowest effective concentration 50 (EC(50)) for oxytocin and prostaglandin F(2alpha). Anatomical differences between ovarian and cervical uterine regions modulate the hormonal regulation of uterine sensitivity to serotonin and prostaglandin F(2alpha) in the non-pregnant rat uterus.

Induction of male sexual behavior by norethisterone: role of its A-ring reduced metabolites.

The estrogenic and androgenic potencies of norethisterone (NET), a synthetic nonaromatizable progestin, and three of its reduced metabolites (5 alpha-NET; 3 alpha, 5 alpha-NET; 3 beta, 5 alpha-NET) were assessed by their ability to restore male sexual behavior in castrated male rats following their chronic administration in combination with either 5 alpha-dihydrotestosterone (DHT) or estradiol (E2), or when given alone. Full restoration of mating was achieved when 3 beta, 5 alpha-NET was administered with DHT, indicating an estrogenic effect of this compound. Lower estrogenic effects were noticed with 3 alpha, 5 alpha-NET and 5 alpha-NET, while NET had very little estrogenic potency. The only effective compound to restore ejaculation, when administered with E2, was NET, indicating its androgen-like intrinsic potency. When administered alone, NET exerted the most potent effect on male behavior, followed by 5 alpha-NET, while the tetrahydro derivatives were ineffective. The observation that NET alone restored male sexual activity at a level identical to that induced by testosterone demonstrated an androgenic-estrogenic activity of this progestin exerted through its intrinsic androgenic effect, and the estrogenic effect of its tetrahydro derivatives. Overall results indicated that the metabolism of NET modulates its mode of action at the brain, and support the concept that both estrogenic and androgenic effects are required for mating activation.

Xanthorrhizol induces endothelium-independent relaxation of rat thoracic aorta.

Xanthorrhizol, a bisabolene isolated from the medicinal plant Iostephane heterophylla, was assayed on rat thoracic aorta rings to elucidate its effect and likely mechanism of action, by measuring changes of isometric tension. Xanthorrhizol (1, 3, 10, 30 and 100 microg/mL) significantly inhibited precontractions induced by KCI-; (60mM), noradrenaline (10(-6) M) or CaCl2 (1.0 mM). Increasing concentrations of external calcium antagonized the inhibitory effect on KCl-induced contractions. The vasorelaxing effect of xanthorrhizol was not affected by indomethacin (10 microM) or L-NAME (100 microM) in intact rat thoracic aorta rings precontracted by noradrenaline, which suggested that the effect was not mediated through either endothelium-derived prostacyclin (PGI2) or nitric oxide release from endothelial cells. Endothelium removal did not affect the relaxation induced by xanthorrhizol on rat thoracic aorta rings, discarding the participation of any substance released by the endothelium. Xanthorrhizol inhibitory effect was greater on KCI- and CaCl2-induced contractions than on those induced by noradrenaline. Xanthorrhizol inhibitory effect in rat thoracic aorta is likely explained for interference with calcium availability by inhibiting calcium influx through both voltage- and receptor-operated channels.

Chemical composition and antispasmodic effect of Casimiroa pringlei essential oil on rat uterus.

The Casimiroa pringlei essential oil was analyzed to determine its chemical composition. Its effect on rat uterine smooth muscle was studied and compared with verapamil. Pure commercial piperitone, eucalyptol, and alpha-terpineol, the major constituents of C. pringlei essential oil, were tested on the uterine tonic contraction induced by high-potassium depolarizing solution (KCl 60 mM).

The ovarian and cervical regions of the rat uterus display a different contractile response to serotonin and prostaglandin F2α I. The estrous cycle

In pharmacological studies using isolated tissues, the sensitivity to different agonists may vary depending on the anatomical region. The aim of the present study was to evaluate the in vitro contractile response to serotonin, prostaglandin F2alpha, and oxytocin of the ovarian and the cervical uterine segments isolated from rats in the four different stages of the rat estrous cycle. Non-cumulative curves were recorded for both, the ovarian and the cervical uterine segments. The cervical portion displayed a higher contractile response to serotonin and a lower response to PGF2alpha than the ovarian portion. Oxytocin induced similar responses in both uterine segments. The uterine ovarian segment displayed a similar sensitivity to serotonin in all the estrous cycle stages, whereas in the cervical segment, influenced by estrogens in diestrus and proestrus, an increase in contractility was observed. According to these findings, serotonin might participate in the spermatozoa transport toward the oviduct. The higher response of the ovarian portion to prostaglandin F2alpha is in line with its role during labor and delivery.

Galphimia glauca organic fraction antagonizes LTD4-induced contraction in guinea pig airways

Galphimia glauca is used for the treatment of asthma and allergies in Latin American traditional medicine. The ethylacetate fraction from its aerial parts was assayed for bronchoconstriction induced by antigen and several agonists in guinea pig tracheae. The organic fraction significantly inhibited the contractile response to ovalbumin in tracheae from sensitized guinea pigs, and significantly and selectively inhibited the bronchoconstriction induced by leukotriene D(4) (LTD(4)). The relative potency of the ethylacetate fraction of G. glauca to produce a concentration-dependent rightward shift of LTD(4) concentration-response curve was similar to that reported for SK&F 104353, a well-known competitive LTD(4)-antagonist.

Optimization of a Pravastatin Quantification Method Using HPLC with Ultraviolet Detection in Human Serum for Monitoring Dyslipidemic Patients

Abstract A high performance liquid chromatography (HPLC) method for the estimation of pravastatin in human serum samples has been developed to monitor dyslipidemic patients. The method was fully validated and validation parameters were in the linearity range 10–200 ng/mL, correlation coefficient 0.99, mean recovery >0.73, quantification limit 10 ng/mL, and limit of detection, 5 ng/mL; this method was applied for pravastatin determination in human serum from Mexican dyslipidemic patients. Pravastatin values found for three studied patients were 73, 57, and <10 ng/mL, indicating the importance of monitoring, due to the metabolic variability of these chronic patients.

Sesquiterpenoids from antidiabetic Psacalium decompositum block ATP sensitive potassium channels.

ETHNOPHARMACOLOGICAL RELEVANCE The hypoglycemic effect of root and rhizome aqueous decoction of Psacalium decompositum (Asteraceae), a medicinal herb from Mexico, has been experimentally demonstrated, leading to the identification of several hypoglycemic sesquiterpenoids, such as cacalol, and the mixture of 3-hydroxycacalolide, and epi-3-hydroxycacalolide; however, the mechanism of action of these compounds is unknown. AIM OF THE STUDY To establish whether cacalol, cacalone epimer mixture and cacalol acetate may block adenosine triphosphate-sensitive potassium channels (K(ATP) channels) in a similar way to the antidiabetic drug glibenclamide. MATERIALS AND METHODS Cacalol, cacalone epimer mixture, and cacalol acetate were tested on the diazoxide-induced relaxation of male rat aortic rings precontracted with phenylephrine (3.2x10(-6)M). RESULTS Cacalol (10(-5)M), cacalol acetate and the cacalone epimer mixture (10(-4)M) inhibited the diazoxide effect, in a similar manner and concentration as glibenclamide (10(-5)M). Cacalone epimer mixture exerted this effect in a concentration-dependent manner (P<0.01). Cacalol (10(-4)M), irreversibly inhibited the diazoxide-induced relaxation, and displayed activity at a lower concentration (10(-5)M) than cacalone epimer mixture and cacalol acetate. CONCLUSIONS These results suggest that the studied compounds block K(ATP) channels in a similar way to glibenclamide in rat aorta. However, controversial data indicate that Psacalium decompositum sesquiterpenoids are less effective than glibenclamide in lowering plasma glucose levels, suggesting that cacalol and cacalone epimer mixture, as well as cacalol acetate, may display a higher affinity to SUR2 subunit of K(ATP) channels in aortic smooth muscle than to SUR1 subunit in pancreatic beta-cells.

The androgenic effect of norethisterone and 5α-norethisterone on the contractile response of the rat vas deferens to methoxamine and serotonin

Norethisterone (NET) and its metabolite 5alpha-norethisterone (5alpha-NET) are competitors for the androgen receptor. The sensitivity of the rat vas deferens to the contractile action of methoxamine and serotonin is regulated by hormonal and anatomical factors. The aim of this study was to evaluate the ability of NET and 5alpha-NET to induce the androgen-regulated contractile response to methoxamine and serotonin in the epididymal and prostatic portions of rat vas deferens. Adult male rats either intact, castrated or steroid-treated castrated were used. The contractility was recorded isometrically, and non-cumulative concentration-response curves to either methoxamine or serotonin were obtained. NET and 5alpha-NET partially restored the sensitivity to methoxamine and serotonin in the epididymal portion of castrated rats. The maximal responses to both agonists were significantly higher than those observed in castrated rats, and significantly lower than the responses observed in either intact or androgen-treated castrated rats. The prostatic portion was less responsive to both agonists than the epididymal portion, in all groups but castrated rats, as castration induced sensitivity to both agonists. NET and 5alpha-NET displayed a partial though similar androgenic activity in the rat vas deferens. These results contrast with previous reports where a decrease of androgenic effect due to the 5alpha-reduction of NET has been found.