Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adenyl cyclases of chick oviduct and rat prostate were not stimulated by estrogen and testosterone, respectively, suggesting that growth and differentiation of these target tissues are not mediated by adenosine 3',5'-monophosphate. Estrogen acutely activated adenyl cyclase in the castrate rat uterus, but this was prevented by administration of DL-propranolol, suggesting that the effect was mediated by catecholamines. Progesterone produced a delayed stimulation of oviduct adenyl cyclase preceding and concomitant with the induction of synthesis of avidin.
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PMID:Steroid hormones: effects on adenyl cyclase activity and adenosine 3',5'-momophosphate in target tissues. 431 7

Interactions of hormones stimulating and inhibiting uterine contraction were studied in vitro in uteri from oophorectomized rats. The beta-adrenergic effector, isoproterenol, a potent inhibitor of contraction, produced a dose-related increase of adenylate cyclase and accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) that was inhibitable by propranolol. Oxytocin, which stimulates contraction, effectively inhibited accumulation of uterine cAMP induced by isoproterenol in the presence or absence of theophylline. Prostaglandins E(2) and F(2alpha), each at a maximum effective concentration of 0.5 muM, also inhibited accumulation of cAMP induced by isoproterenol, consistent with their effect in stimulation of uterine contraction. Prostaglandin E(2), but not prostaglandin F(2alpha), stimulated cAMP accumulation in a dose-related manner at concentrations in excess of 0.5 muM. Neither propranolol nor oxytocin inhibited that response. Bovine endometrial adenylate cyclase failed to respond to isoproterenol but was stimulated by prostaglandins E(1) and E(2). When myometrial preparations were studied, isoproterenol stimulation and prostaglandin effects were observed as for whole castrate uterus. The competitive physiological actions of beta-adrenergic effectors on the one hand, and oxytocin and prostaglandins on the other hand, are based on their influences on a myometrial adenylate cyclase. Stimulation of uterine cAMP accumulation by prostaglandin E(2) is due to action at a different and unrelated site.
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PMID:Hormonal interactions in the uterus: inhibition of isoproterenol-induced accumulation of adenosine 3':5'-cyclic monophosphate by oxytocin and prostaglandins. 434 7

Clinical research has shown that prostaglandins (PGs) play an important role in every phase of human reproduction. The logical consequence of early basic biological research into PGs is the current interest in clinical evaluation of PGs as agents to induce labor and abortion and to stimulate menstruation. This is a review of the current literature dealing with PG research. Both PGF2alpha and PGE2 are known to induce labor at term when administered by intravenous infusion. Their relative effectiveness as compared to oxytocin has yet to be assessed. Intravenous infusion of PGE1, PGE2, and PGF2alpha will also induce abortion. Current research is being directed toward finding more practical methods of administration than continuous intravenous infusion. There is hope that PGs will be able to be used as a once a month contraceptive administered at the time of expected menstruation following exposure and a possible unwanted pregnancy. The exact mechanism of action of PGs on smooth muscle is still largely unknown. The differences in response of a specific muscle to different PGs have also not received much research attention. Little is known, for example, regarding the action of PGs on the cervix as opposed to the rest of the uterus. Particularly unknown is the mechanism of action of PGs at the molecular level. In most of the situations studied, PGs seem to stimulate adenyl cyclase activity and cyclic adenosine monophosphate formation or accumulation.
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PMID:Developing applications of prostaglandins in obstetrics and gynecology. 462 50

Research on the physiopathologic and biochemical nature of prostaglandins (PGs) suggest that PGs play a role in reproductive physiology. In vitro studies show that the PGE series decrease the motility of the human uterus, fallopian tubes, and ureter, and produce vasodilatation. PGFs cause vasoconstriction and increased motility of the uterus, fallopian tubes, ureter, and gastrointestinal muscle. PGs are also known to inhibit lipolysis, platelet aggregation, and gastric secretion. The exact mechanism of PGs are not fully understood, but evidence suggests that many responses can be attributed to interference with the enzyme adenyl cyclase, which catalyzes the formation of adenosine 3',5'-monophosphate (cyclic AMP) from adenosine triphosphate. The adenyl cyclase-cyclic AMP system mediates lipolysis, steroidogenesis, gastric secretion, certain smooth muscle motility responses, and increase in permeability due to vasopressin. Early studies of the myometrial effects of PGs showed that the PGE series inhibited the motility of the human myometrium in vitro while the PGF series produced mixed responses. The role of PGF2alpha in parturition has not been established but evidence suggests that it has a potential role as an oxytocic in cases of therapeutic abortion. In the area of human fertility, the physiologic role of PGs in seminal fluid is hypothesized to facilitate the migration of spermatozoa from the vagina into the uterine cavity. Karolinska Institute researchers have found that some infertile males have low PG levels in their ejaculates and are now working with methods of improving the PG levels to improve their fertility. Pickles et al. proposed a potential role for PGs in the etiology of dysmenorrhea, having found a significantly higher ratio of PGF to PGE in a series of patients with severe dysmenorrhea than in a comparable series of normal patients. The luteolytic and antinidatory effects of PGF2alpha are being investigated and studies appear encouraging. PGs have therapeutic potentials in induction of labor, treatment of infertility, morning-after conception, treatment of dysmenorrhea, and contraception by alteration of fallopian tube motility.
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PMID:The role of prostaglandins in reproductive physiology. 491 53

Prostaglandin E2 (PGE2) increased the force of the spontaneous contractions of the rat myometrium and decreased the sensitivity of the uterus to the relaxing effects of the specific beta-adrenergic catecholamine agonist isoprenaline. Prostaglandin E2, at concentrations above 10 mumol/l, increased cyclic AMP production by intact muscle strips. The muscle strips were far more sensitive, however, to the inhibitory effect PGE2 had on isoprenaline-dependent cyclic AMP production (threshold less than 0.001 nmol/l). Both PGE2 and isoprenaline stimulated adenylate cyclase activity of a myometrial subcellular (particulate) fraction in a guanyl nucleotide-requiring manner. When present in saturating concentrations (100 mumol/l), the stimulatory effects were not additive, suggesting that the receptors for the two agonists competed for the same catalytic subunit of adenylate cyclase or for the same guanyl nucleotide-requiring factor which couples receptors and enzyme. If muscle strips were incubated with PGE2 before the preparation of the adenylate cyclase-containing particulate fraction, the enzyme became less responsive to stimulation by guanyl nucleotide and by isoprenaline and PGE2 in the presence of guanyl nucleotide. The PGE2 receptor may therefore interact with the beta-adrenoreceptor to inhibit isoprenaline-dependent cyclic AMP production by intact muscle cells by desensitizing adenylate cyclase, possibly at the level of the guanyl nucleotide-dependent coupling step.
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PMID:Interaction of prostaglandin E2 and beta-adrenergic catecholamines in the regulation of uterine smooth muscle motility and adenylate cyclase in the rat. 609 May 68

Estradiol is demonstrated to induce histidine decarboxylase, and histamine is shown to activate adenylate cyclase in rat uterus. Histamine and cyclic 3',5'-AMP mimic the effects of estradiol in that they enhance RNA synthesis, induce glycolytic enzymes and uterus imbibition. The data suggest that estradiol enhances by induction of histidine decarboxylase the formation of histamine, the latter activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes through phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol histamine and cyclic 3',5'-AMP among uterus cells. Autoradiography has shown that [3H]-estradiol is bound by the nuclei of myometrium cells, [3H]-histamine was found above the cytoplasm of these cells, E13H]-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread effect of hormone on cells of different types which form together a kind of multicellular functional system.
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PMID:Multistage functional system amplifying and spreading the effect of estradiol in rat uterus. 624 14

Porcine relaxin produced a rapid, dose-related rise of cyclic AMP values in rat uterine tissue incubated in vitro. In time-course experiments, peak cyclic AMP concentrations were observed in the uterine slices at 5 min; subsequently the values fell, at first rapidly and then more slowly with the tissue concentration remaining significantly raised at 15 min. Levels of cyclic GMP in the same tissue slices were not significantly altered by relaxin. Furthermore, no increase in basal cyclic AMP values was measured in control slices prepared from the rat heart or jejunum. An increase in cyclic AMP concentration comparable to that found in the rat uterus was observed in slices of porcine uterus and cervix but not of vagina when they were stimulated with porcine relaxin. Our results suggest that the hormonal action of relaxin on the uterus and cervix is mediated through receptors linked to the enzyme, adenylate cyclase.
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PMID:Modulation of cyclic AMP in isolated rat uterine tissue slices by porcine relaxin. 625 89

Imidazole, at concentrations between 10(-3) and 10(-2) M, exerts a profound stimulatory effect on rabbit uterine strips obtained during pregnancy and studied isometrically in vitro. The action is not duplicated by N-alkylimidazoles which have greater potency as inhibitors of thromboxane synthetase but the effect of imidazole was antagonized by isoproterenol or theophylline. Biochemical analysis indicated that imidazole at concentrations greater than 5 x 10(-4) M stimulated both high and low affinity forms of cyclic AMP phosphodiesterase. The uterus of pregnant rabbits is profoundly refractory to any kind of pharmacological stimulation and the effects of imidazole, acting to stimulate phosphodiesterase, suggest that the integrity of the adenyl cyclase-cyclic AMP-protein kinase system is a necessary requirement for this organ to remain quiescent during pregnancy.
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PMID:Enhanced excitability of the uterus of the pregnant rabbit by imidazole stimulation of cyclic AMP phosphodiesterase. 625 37

The identification and characterization of histamine receptors in the organ systems of various species has been made possible in recent years by the introduction of relatively selective agonists and antagonists of H1 and H2 receptors. H2 receptors have now been clearly demonstrated in gastric mucosa, heart, rat uterus, brain, and adipose tissue. Less well-defined H2 receptor systems have also been described in the vasculature, bronchioles, and other smooth muscles as well as in the thyroid gland and lymphocytes. In tissues where it has been examined a close correlation between H2 receptors and the adenylate cyclase--cyclic AMP system has been found. With the exception of the central nervous system stimulation of H1 receptors does not seem to be involved with cyclic AMP. In the case of the brain the H1 receptor stimulation of adenylate cyclase can be differentiated from H2 receptor stimulation of the enzyme by the use of blocking agents and by the fact that the H1 receptor response is enhanced in the presence of adenosine. Studies of the involvement of histamine with the adenylate cyclase--cyclic AMP system have been concentrated on such tissues as gastric mucosa, heart, rat uterus, brain, and adipose tissue. The present review will concentrate on the literature concerning those tissues.
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PMID:Histamine receptors and cyclic AMP. 625 56

A new potent vasodilator, nicardipine hydrochloride inhibited oxytocin-induced contraction of rat uterus dose-dependently with an increase in the intracellular cyclic AMP level at the onset of relaxation. Dibutyryl cyclic AMP and papaverine, an inhibitor of cyclic AMP phosphodiesterase (PDEase), also inhibited the contraction. Nicardipine inhibited competitively PDEase in homogenates of rat uterus which exhibited apparently two Km values for cyclic AMP (3.6 micro M and 67.3 micro M) with the Ki of 5.3 micro M and 13.2 micro M, respectively, but had no effect on adenylate cyclase. Nicardipine enhanced calcium uptake by rat uterine microsomes, at concentrations which inhibited oxytocin-induced contraction in the same manner as cyclic AMP. The maximal stimulation by nicardipine of the microsomal calcium uptake was identical substantially to that by cyclic AMP, and both were not additive. Cyclic AMP was also accumulated during the uptake reaction in the presence of nicardipine. On the contrary, neither myosin ATPase nor microsomal Ca2+-dependent ATPase was inhibited directly by nicardipine. These results suggest that the inhibition of oxytocin-induced contraction of rat uterus by nicardipine may be due to an enhancement of microsomal calcium uptake, mediated by cyclic AMP accumulated through the inhibition of PDEase.
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PMID:A possible mechanism for relaxation of rat uterine smooth muscle by nicardipine hydrochloride (YC-93), a new potent vasodilator. 627 30


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