Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of pretreatment with pertussis toxin (50-200 micrograms kg-1, i.p.) on the pre-junctional inhibitory actions of the alpha 2-adrenoreceptor agonist xylazine were examined by employing the pithed rat and rat isolated vas deferens. 2. In pithed rats, pertussis toxin attenuated the pressor response to xylazine, but did not alter the pre-junctional cardio-inhibitory actions of xylazine. In epididymal portions of rat vas deferens, pretreatment with pertussis toxin did not alter the pre-junctional inhibitory action of xylazine. 3. These data lend no support for the view that alpha 2-adrenoreceptor-mediated prejunctional inhibition involves inhibition of adenylate cyclase through the Ni regulatory protein, at least in the tissues examined.
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PMID:Pertussis toxin and pre-junctional alpha 2-adrenoreceptors in rat heart and vas deferens. 284 45

Cyclic AMP has been implicated as a regulator of capacitation, but the control of its metabolism in sperm remains obscure. A recent study of mouse sperm has shown capacitation-related changes in the activities of both adenylate cyclase, which increased during incubation, and cyclic nucleotide phosphodiesterase, which decreased. The present study was conducted to extend these observations by measuring phosphodiesterase activity in sperm incubated in media with modified calcium and/or glucose content, conditions known to modulate fertilizing ability. Phosphodiesterase activity of sequential sperm samples, taken first when sperm are essentially uncapacitated and then when they are either partially or completely capacitated, decreased with time under all conditions, and in each case the greater fall in activity was seen in the medium that would support the greater change in fertilizing ability of the sperm population. Sperm washed by centrifugation to remove epididymal fluid also displayed a reduction in phosphodiesterase activity with time. The medium surrounding the sperm contained about half of the total phosphodiesterase activity, as well as 5'-nucleotidase and adenosine deaminase. The crude enzyme preparation showed complex kinetic behavior when assayed over a range of cAMP concentrations, but the reduction in activity with time was seen at all substrate levels. The observed changes in phosphodiesterase activity, together with the increased adenylate cyclase activity seen under these sperm incubation conditions, would increase cAMP availability with time, thus providing further evidence for a fundamental role for cAMP in controlling the events of capacitation.
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PMID:Phosphodiesterase activity of mouse sperm incubated under conditions that modulate fertilizing potential in vitro. 285 27

Insulin antagonized the lipolytic actions of epinephrine in rat epididymal adipocytes when the phosphodiesterase inhibitor, Ro 20-1724, was present. Adipocytes were depleted of functional cAMP by inhibiting adenylate cyclase with N6-phenylisopropyladenosine in the presence of adenosine deaminase such that Ro 20-1724 no longer stimulated lipolysis. The cAMP analogs 8-thioisopropyl-cAMP or 8-thiomethyl-cAMP, which are resistant to phosphodiesterase hydrolysis, were subsequently added to bypass adenylate cyclase and phosphodiesterase action. Under these conditions, insulin antagonized the lipolytic effects of these analogs, even in the presence of Ro 20-1724.
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PMID:The antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. 298 Nov 81

Bicarbonate ion, the local anesthetics procaine and dibucaine, and the ionophores monensin and nigericin have been shown to markedly increase the ability of agents that elevate cyclic adenosine monophosphate (cAMP) levels to initiate motility in bovine caput spermatozoa. A number of other weak bases, including theophylline, D-600 and dipyridamole, elevate cAMP levels maximally in caput sperm at low levels but induce motility only at high levels. These compounds thus appear to have a dual role in the initiation of motility, i.e., they elevate both cAMP levels and internal pH. Confirmation of this view was provided by the demonstration that bicarbonate ion and procaine permit initiation of motility by theophylline, D-600 and dipyridamole at markedly reduced levels. Also, forskolin (a neutral adenylate cyclase activator) elevates cyclic AMP levels in caput sperm but initiates motility only in the presence of bicarbonate or procaine, and the membrane-permeant cAMP analogue 8-bromo-cAMP is capable of inducing motility only in the presence of bicarbonate. Thus, motility in caput sperm is induced only under conditions that elevate both intracellular cAMP and pH, whereas caudal sperm motility is stimulated by an elevation of either cAMP or pH. These data suggest that the epididymal development of motility requires a maturational increase in internal pH. This suggestion was confirmed by direct measurement of the internal pH of caput and caudal sperm; the internal pH of the former was found to be 5.84 +/- 0.1 and the latter 6.27 +/- 0.05.
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PMID:Evidence for a role for cellular alkalinization in the cyclic adenosine 3',5'-monophosphate-mediated initiation of motility in bovine caput spermatozoa. 298 38

The mixed adrenergic agonist epinephrine, at a 10 microM concentration, stimulated cyclic AMP production and glycerol release in the epididymal adipose tissue of ob/ob male mice. These effects when tested, respectively, after 7 min in the presence and after 60 min in the absence of theophylline were, however, 7- and 5-fold lower than in lean controls. The alpha-adrenergic blocker phentolamine and adenosine deaminase (which destroys extracellular adenosine) did not restore a normal lipolytic response to epinephrine in the adipose tissue of ob/ob mice. These data provide indirect evidence against a hyperactive mechanism in the coupling of alpha-adrenergic receptors and adenosine receptors to Ni, the guanine nucleotide-binding inhibitory component of adenylate cyclase, as the cause of reduced lipolysis in the adipose tissue of ob/ob mice.
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PMID:Indirect evidence against a contribution of the guanine nucleotide-binding inhibitory component of adenylate cyclase to impaired lipolysis in the epididymal adipose tissue of congenitally obese (ob/ob) mice. 299 42

To investigate dobutamine-induced cardiac adaptations, we compared dobutamine-treated with swim-trained and sedentary control rats. After 14 wk of treatment, heart rate was lower in the dobutamine-treated (279 +/- 6) and exercise-trained (287 +/- 4 beats/min) groups than in the control animals (305 +/- 3 beats/min; P less than 0.05). The exercised rats gained less weight (164 +/- 11 g; P less than 0.05) than the dobutamine-treated (238 +/- 16 g) and the control animals (231 +/- 12 g). Also, compared with the two other groups, the exercise group had higher relative heart weights (3.47 +/- 0.08 vs. 2.82 +/- 0.06 and 2.90 +/- 0.05 g/kg in the dobutamine and control groups, respectively; P less than 0.05) and lower epididymal fat pad weights (6.6 +/- 0.4 vs. 13.3 +/- 1.0 and 11.4 +/- 0.5 g/kg in the dobutamine and control groups, respectively; P less than 0.05). However, both the maximum heart rate produced by isoproterenol and the isoproterenol dose producing 50% of the peak heart rate response were similar among the three groups. Myocardial norepinephrine content, beta-adrenergic receptor number, and adenylate cyclase activation by isoproterenol, NaF, 5'-guanylyl imidodiphosphate, and forskolin also did not differ. Thus, although there were differences between the dobutamine-treated and the exercised rats, the two groups were similar in that they developed bradycardia that was not due to cardiac adrenergic desensitization.
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PMID:Dobutamine-induced cardiac adaptations: comparison with exercise-trained and sedentary rats. 301 Jul 40

Adipocytes contain adenosine receptors, termed A1 receptors, which inhibit lipolysis by decreasing adenylate cyclase activity. The inhibition of lipolysis by adenosine agonists in vivo acutely suppresses the plasma concentrations of free fatty acids (FFA) and triglycerides. We have found that infusions of the adenosine receptor agonist phenylisopropyladenosine (PIA) initially decreases plasma FFA concentrations; however, with prolonged exposure (6 d), rats become very tolerant to the effects of the drug. Adipocytes isolated from epididymal fat pads from PIA-infused rats have altered lipolytic responses. When lipolysis is stimulated with a relatively high concentration of isoproterenol (10(-7) M), PIA does not inhibit lipolysis in adipocytes from the infused animals. However, PIA inhibits isoproterenol-stimulated cyclic AMP (cAMP) accumulation in adipocytes from the infused rats although with decreased sensitivity compared with controls. The explanation for the impaired antilipolytic effect appears to be due to the fact that isoproterenol-stimulated cAMP accumulation is markedly increased in cells from infused rats. Indeed, basal lipolysis and lipolysis stimulated with lower concentrations of isoproterenol (10(-9), 10(-8) M) are effectively inhibited by PIA. cAMP accumulation is greatly increased in adipocytes from infused rats when stimulated by isoproterenol, ACTH, and forskolin. The results have some striking analogies to changes induced in nerve cells by prolonged exposure to narcotics. These data suggest that tolerance to PIA develops in adipocytes as a consequence of enhanced cAMP accumulation.
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PMID:Desensitization of adenosine receptor-mediated inhibition of lipolysis. The mechanism involves the development of enhanced cyclic adenosine monophosphate accumulation in tolerant adipocytes. 301 37

Mature porcine sperm preserved in the cauda epididymis are quiescent. At ejaculation, they are mixed with the seminal vesicle fluid containing HCO3- and are rapidly activated. The role of HCO3- on the sperm activation process at ejaculation was studied in vitro. HCO3- quickly increased the motility, respiration rate and cAMP content of the porcine epididymal sperm. The extent of activation was proportional to the pCO2 in the medium. The activating effect of HCO3- on the motility was observed even in the absence of fructose as well as in the presence of KCN. 8-Bromoadenosine 3',5'-cyclic monophosphate and theophylline showed similar activating effects to that of HCO3-. However, HCO3(-)-free seminal plasma, Ca2+, amino acids, intermediates of the Krebs cycle, substrates of respiration and increases in the intracellular pH, extracellular pH or ionic strength of the medium had no effect. Fructose sustained the active state of the sperm and gradually increased both the motility and respiration rate when the dose of HCO3- was low. The anion channel blocker enhanced the activating effect of HCO3-. These results suggest that, upon ejaculation, HCO3- is a unique activator in vivo which makes the quiescent sperm motile via the HCO3(-)-adenylate cyclase-cAMP system, to which an endogenous HCO3- derived from metabolic CO2 may be related.
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PMID:The activating effects of bicarbonate on sperm motility and respiration at ejaculation. 303 42

Previously, the antilipolytic effect of prostaglandin E2 (PGE2) has been investigated in conventional adipocyte incubations. To define the effect of PGE2 on lipolysis more clearly, isolated epididymal adipocytes were studied with the perifusion system. PGE2 inhibited isoproterenol (100 nM)- and theophylline (1 mM)-stimulated lipolysis in a concentration-dependent manner in both the perifusion system and conventional incubations. However, the half-maximally inhibitory concentration (ED50) of PGE2 on isoproterenol-induced lipolysis was about 0.4 nM in the perifusion system, whereas the ED50 was 8 nM in the static adipocyte incubations. The ED50 values of PGE2 on theophylline-induced lipolysis were 0.8 nM (perifusion) and 5 nM (incubation), respectively. Thus, the sensitivity of stimulated lipolysis to PGE2 was about 10 times higher in the perifusion system than in conventional adipocyte incubations. In addition, the maximal antilipolytic effect of PGE2 was greater in the perifusion system. At a concentration of 100 nM PGE2 inhibited theophylline-induced lipolysis by 82 +/- 5% in adipocyte incubations, whereas lipolysis was inhibited by 100 +/- 3.5% in the perifusion system (P less than 0.05). When lipolysis was stimulated by isoproterenol the maximal antilipolytic effect of PGE2 was an inhibition of 90 +/- 2.5% in the perifusion system and 55 +/- 5% in adipocyte incubations (P less than 0.05). Moreover, the maximal antilipolytic effect was obtained at a PGE2 concentration of 20 nM in the perifusion system, but at a concentration of 100 nM in static incubations. The release of immunoreactive PGE2 from adipocytes was measured by RIA. In the perifusion system no PGE2 could be detected in the effluent under basal conditions; however, during exposure to 100 nM isoproterenol a small amount of PGE2 was detected (3-4.5 pg/10(6) cells X min). Exogenous PGE2 was almost totally (90%) recovered in the effluent. In adipocyte incubations basal PGE2 production was 103 +/- 22 pg/10(6) cells X 60 min, whereas both isoproterenol and theophylline increased these amounts of PGE2 2-fold (P less than 0.01). It is concluded that exogenous PGE2 has pronounced antilipolytic properties at very low concentrations (subnanomolar) in perifused adipocytes. The reduced sensitivity and maximal responsiveness of PGE2 in static incubations may be related to accumulation of FFA and endogenous PGs, which may partially obscure the interaction of exogenous PGE2 with the adenylate cyclase complex.
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PMID:Antilipolytic effect of prostaglandin E2 in perifused rat adipocytes. 330 32

The purpose of this study was to determine the localization of calmodulin in the developing mouse testis by the indirect immunoperoxidase method. In addition, the amount of calmodulin in pachytene spermatocytes, spermatids, and residual bodies isolated from the mouse testis and epididymal spermatozoa was quantitated by the adenylate cyclase activation assay and by enzyme immunoassay. The relative levels of calmodulin in the developing mouse testis and in the isolated testicular germ cells were confirmed by western transfer staining. The level of immunoreactive calmodulin was very low in the testes from immature animals. In testes from the mature mouse, calmodulin was found to be localized in spermatocytes and spermatids, but was not found in spermatogonia, Sertoli cells, and interstitial cells. By contrast, immunochemical staining of tubulin was extremely intense in Sertoli cells. Biochemical determinations also showed that pachytene spermatocytes, round spermatids, spermatozoa, and residual bodies contained 14.9 micrograms, 15.8 micrograms, 2.3 micrograms and 5.2 micrograms of calmodulin per mg of protein, respectively. Both the immunochemical and the biochemical studies revealed that levels of calmodulin were high in the spermatocytes and in the round spermatids, as compared to the level in spermatozoa. This fact strongly suggests that the large amount of calmodulin in mammalian testes may be associated primarily with meiotic divisions and/or spermatogenesis.
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PMID:Immunohistochemical study of calmodulin in developing mouse testis. 354 67


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