The interactions between SK&F 104078 and several selective alpha 2-adrenoceptor agonists at pre- and postjunctional alpha 2-adrenoceptors were investigated in order to assess the previously reported selectivity of SK&F 104078 for postjunctional alpha 2-adrenoceptors and to determine whether or not SK&F 104078 could uncover subtypes of alpha 2-adrenoceptors located prejunctionally as has also been suggested. The alpha 2-adrenoceptor agonists, UK 14,304, xylazine, B-HT 933, B-HT 920, clonidine and M-7, produced concentration-dependent prejunctional alpha 2-adrenoceptor-mediated inhibition of neurogenic responses in the guinea pig atrium and rat vas deferens and produced postjunctional alpha 2-adrenoceptor-mediated contraction of the canine saphenous vein. The alpha 2-adrenoceptor antagonist, rauwolscine, blocked all the agonists at both pre- and postjunctional alpha 2-adrenoceptors without demonstrating preference for any agonist or any synaptic location of alpha 2-adrenoceptors. In marked contrast, SK&F 104078 produced equivalent antagonism of all agonists in the canine saphenous vein but had no significant effect against the same agonists in the guinea pig atrium, suggesting a high degree of selectivity for postjunctional alpha 2-adrenoceptors in these test systems, consistent with our previous observations. In the rat vas deferens, however, SK&F 104078 significantly antagonized the prejunctional alpha 2-adrenoceptor-mediated effects of clonidine and M-7 but did not block the responses to UK 14,304, xylazine, B-HT 933 and B-HT 920. These results indicate that the prejunctional alpha 2-adrenoceptor antagonist effects of SK&F 104078 are tissue and agonist dependent, and that there may be at least two subtypes of prejunctional alpha 2-adrenoceptors that can be discriminated with SK&F 104078 but not with rauwolscine. Both subtypes of prejunctional alpha 2-adrenoceptors may be present in the rat vas deferens, while only the SK&F-104078-insensitive subtype is present in the guinea pig atrium.
Objective: To study reactivity of the ovarian vascular bed to noradrenaline and carbachol during an experimentally induced ovarian hyperstimulation syndrome (OHSS) in rabbits. Materials and Methods: Rabbits were treated with human menopausal gonadotropin (75 IU) daily for 6 days, followed by human chorionic gonadotropin (2,500 IU) to induce OHSS. The ovarian vascular bed was isolated and perfused with physiological solution and its reactivity to injected noradrenaline and acetylcholine was examined. Results: The mean weight of the hyperstimulated ovary was 2.85 ± 0.5 g compared to 0.25 ± 0.1 g for the control rabbits. There was no significant difference in (a) the basal perfusion pressure of the ovarian vascular bed ex vivo; (b) the potency of, or maximum response to, noradrenaline, and (c) agonist dissociation constant or receptor density. Carbachol induced significantly greater vasodilation in ovarian vascular beds from hormone-treated rabbits, indicating a greater role for nitric oxide in this syndrome, as further supported by the observation that NW-nitro-L-arginine methyl ester hydrochloride (L-NAME) was more effective against carbachol-induced response in hormone-treated rabbits. Conclusion: In the rabbit model of OHSS, carbachol produced an increased ex vivo vascular response but noradrenaline did not.
In the rat anococcygeus muscle, diazepam (1.8 X 10(-6) - 2.8 X 10(-5) M), dipyridamole (2 X 10(-6) - 3.2 X 10(-5) M) and ATP (2 X 10(-4) - 6.4 X 10(-3) M) concentration-dependently inhibited the motor response to field stimulation. Glycine (up to 7.5 X 10(-3) M) and GABA (up to 10(-4) M) had no effect on field stimulation. Concentrations of diazepam and dipyridamole which reduced motor response to field stimulation did not relax the tonically contracted rat anococcygeus muscle. However, at these concentrations, diazepam and dipyridamole potentiated the inhibitory responses of the tonically contracted rat anococcygeus muscle to ATP and field stimulation. It is suggested that diazepam and dipyridamole reduced the motor response to field stimulation by potentiating the inhibitory transmitter released during nerve stimulation. Also, since the time-course of the effect of diazepam and dipyridamole on the inhibitory responses to ATP and field stimulation are closely similar, the results would tend to provide additional support for the concept of purinergic transmission in the rat anococcygeus muscle.
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