Influence of steroid ovarian hormones and calcium on drug-induced contractions of the isolated immature uterine muscle of mouse. An analysis of histamine receptor system.

1. Through the relative responsiveness (rho) determined for histamine (Hist), oxytocin (Oxy) and acetylcholine (Ach) in prepuberal untreated, estrogen, and estrogen plus progesterone dominated uteri of mouse, it was possible to measure the capability of each receptor system, which mediates responses induced by these agonists. 2. In all cases values of rho for Hist were lower than those for Ach and Oxy independently of hormone treatment and calcium concentrations used (0.2 or 2.0 mM), suggesting that the ability of histamine receptor system to promote contraction of mouse uterus is less effective than those mediating responses induced by other agonists studied here. 3. A comparison between the present data with those previously reported for dog uterus showed marked differences in the abilities of the histamine receptor system to mediate histaminergic stimulus in myometrium of two different animal species. 4. The author suggests that genetic characteristics controlling the development of a given receptor system can play a role regulating physio-pharmacological actions of drugs in the myometrium.

Evidence for multiple sources of calcium involved on the contractile effects of agonists in the dog uterus. Influence of ovarian sexual hormones.

We compared the characteristics of Ca2+ pools involved in the contractile effect of acetylcholine (Ach), histamine (Hist), oxytocin (Oxy) and barium (Ba2+) in prepuberal untreated or estrogen plus progesterone dominated uteri. After Ca2+ (0.2 mM) withdrawal different rates of decay for cited agonists were observed. If Ca2+ concentration was increased to 2.0 mM before the Ca2+ withdrawal, the t 1/2 for Ach and Hist were markedly increased. Hormonal treatment significantly increase the rate of decay for all agonists except for Ba2+ independent of the initial Ca2+ concentration, suggesting that in this condition the tightly bound Ca2+ is absent.

Differential sensitivity of major types of opioid binding sites to U.V. irradiation.

The three major types of opioid binding sites exhibited differential sensitivity to inactivation by ultraviolet irradiation. The order of sensitivity was delta greater than mu greater than kappa. Two separate rates of inactivation by U.V. light were observed for each type, an initial fast rate and a secondary slow rate. Addition of EDTA or EGTA to the buffer medium decreased only the initial fast rate of inactivation. The photosensitive tryptophan and tyrosine moieties have been shown to be photolyzed in a two step manner in a number of protein systems. It is suggested that the differential sensitivity of the multiple opioid binding sites may reflect either differing amino acid composition or differences in tertiary structure.

Influence of castration of the neonatal rat on the contractile effects of barium chloride and adrenaline in isolated vas deferens: the role of calcium.

Time-response curves to maximal concentrations of barium chloride (BaCl2) (3 X 10(-2) M) and adrenaline (10(-4) M) were studied in vasa deferentia from 3-month-old rats castrated at birth. Either barium or adrenaline was left in the organ baths for 5-min periods, at intervals of about 30 min, and the corresponding isotonic contractions recorded. Two types of effects were measured: the fade response (Jurkiewicz et al., 1977) and the rate at which responses were reduced after Ca2+ withdrawal from nutrient solution. The fade response for BaCl2 was strikingly greater than that in controls. When calcium was removed from the nutrient solution, an almost complete loss of the response to BaCl2 was achieved in less than 3 min for preparations of 3-day castrates, in about 40 min for the organs of 15-day castrates, and in more than 140 min for normal preparations. Treatment with testosterone, 1 week before the experiments, abolished the fade response to BaCl2 and antagonized the loss of responsiveness observed for this substance in a calcium-deficient solution. These data suggest that the production of testosterone by the testis during the critical period of neonatal differentiation is important for the translocation of calcium ions in the isolated vas deferens of the adult rat.

Inhibitory effects of ketamine on the isolated uteri of the rat: evidence for the mechanism of action.

The inhibitory effect of ketamine on the agonist-induced contraction of isolated rat uteri was compared with that of papaverine and verapamil. Under similar experimental conditions papaverine and verapamil were found to be more potent than ketamine. When preparations were preincubated for 20 min with either ketamine (3 X 10(-5) to 10(-3) M) or papaverine (10(-6) to 10(-5) M), a noncompetitive antagonism was observed against oxytocin with pD'2 values of 3.67 +/- 0.07 and 5.13 +/- 0.10, respectively. A noncompetitive form of antagonism was also observed by papaverine against BaCl2 with pD'2 values of 4.59 +/- 0.15, while ketamine produced competitive antagonism with a pA2 value of 4.68 +/- 0.12. It was also demonstrated that all three inhibitory drugs interfere competitively with Ca2+ on the rat uteri. However, ketamine was shown to be less potent than verapamil and papaverine in antagonizing the effects owing to an increased Ca2+ concentration in the medium. These results are consistent with previous publications that ketamine has a papaverinelike effect on the rat uteri and suggest that the relaxation promoted in this preparation is due, at least in part, to blockade of the Ca2+ translocation processes.

Effects of neonatal androgenization upon the pharmacological reactivity of dog uteri.

The influence of androgen treatment during the neonatal period on the contractions induced in dog uteri by acetylcholine, oxytocin, histamine and barium chloride was studied in vitro. An increase in the sensitivity of preparations was observed to acetylcholine and oxytocin, represented by leftward shifts in the ED50 values of these agonists. On the other hand the ED50 values for histamine and barium chloride remained unchanged. The relative responsiveness (p) remained unaltered for all the agonists studied. These effects differ from those observed in the uterus of neonatally androgenized female rats.

Bone formation in the clitoris of neonatallu testosterone treated female dogs.

O tratamento precose de cachorrinhas no 1o. e 3o. dias de vida com propianato de testosterona provoca crescimento do clitoris que se apresenta com aspecto penisoide Por outro lado a castracao pos-natal de cachorrinha impede a evolucao da estrutura ossea peniana. Estes resultados falam a favor da hipotese de que tanto o clitoris como o penis caninos apresentam a mesma potencialidade de resposta ao estimulo androgenico

Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs.

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.

Influence of photoperiodism on cannabinoid content of Cannabis sativa L.

Cannabis sativa plants submitted to 10 and 12 hours of natural light showed different content in cannabinoids. An increase of exposure to natural light of only 2 hours a day, at least, doubled the average amoung of THC, but decreased that of cannabichromene.