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

---

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

The proximal tubule of the kidney represents an important location where adenylate cyclase regulates salt and water transport; yet a detailed characterization of the distribution and classification of guanine nucleotide-binding protein (G protein) and adenylate cyclase is lacking. We used purified brush border (20-fold) and basolateral membranes (14-fold) to characterize parathyroid hormone- and G protein-regulated adenylate cyclase and G-protein distribution. Adenylate cyclase was predominantly localized to basolateral membranes, while the 46-kDa alpha subunit of the stimulatory G protein (Gs) was 2-fold higher in brush border membranes than in basolateral membranes. The alpha subunit of the inhibitory G protein (Gi; 41 kDa) was equally distributed on immunoblotting but was 2-fold higher in brush border membranes than in basolateral membranes on radiolabeling with pertussis toxin. A 42-kDa cholera toxin substrate that cross-reacted with antisera to the common alpha subunit of G proteins and to Gs on immunoblotting and that was not immunoprecipitated with two Gi antisera was the most abundant alpha subunit and comprised approximately 1% of the total membrane proteins. These observations suggest that G proteins are important regulators of proximal tubular transport independent of adenylate cyclase.
...
PMID:Proximal tubular epithelial cells possess a novel 42-kilodalton guanine nucleotide-binding regulatory protein. 212 Jul 2

(Rp)-Adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) is a highly specific antagonist of the cAMP-dependent protein kinase from eukaryotic cells and is a very poor substrate for phosphodiesterases. It is therefore a useful tool for investigating the role of cAMP as a second messenger in a variety of biological systems. Taking advantage of stereospecific inversion of configuration around the alpha-phosphate during the adenylate cyclase reaction, we have developed a method for the preparative enzymatic synthesis of the Rp diastereomer of adenosine 3',5'-monophosphorothioate ((Rp)-cAMPS) from the Sp diastereomer of adenosine 5'-O-(1-thiotriphosphate) ((Sp)-ATP alpha S). The adenylate cyclase from Bordetella pertussis, partially purified by calmodulin affinity chromatography, cyclizes (Sp)-ATP alpha S approximately 40-fold more slowly than ATP, but binds (Sp)-ATP alpha S with about 10-fold higher affinity than ATP. The triethylammonium salt of the reaction product can be purified by elution from a gravity flow reversed-phase C18 column with a linear gradient of increasing concentrations of methanol. Yields of the pure (Rp)-cAMPS product of a synthesis with 2 mg of substrate are about 75%.
...
PMID:Enzymatic synthesis of the cAMP antagonist (Rp)-adenosine 3',5'-monophosphorothioate on a preparative scale. 217 77

It has been demonstrated that the adenylate cyclase activity of vascular smooth muscle regulates its tonus. The present study was undertaken to examine adenylate cyclase activity in early and established deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Early and established DOCA/salt hypertensive rats were prepared by injecting 30 mg of DOCA weekly for 3 and 10 weeks, respectively, into male Wistar rats given drinking water with 1% saline. The membrane protein fraction medium containing the protein, 50 microM isoproterenol, 100 microM GTP, 50 microM forskolin or 25 microM calmodulin was applied. The adenylate cyclase activity was determined by a modified method developed in our laboratory using double isotope counting. The adenylate cyclase activity in the early DOCA/salt hypertensive rats was significantly higher (p less than 0.05) than that in the control rats in the basal condition, which was unaffected by additions of isoproterenol, GTP or forskolin. There was no significant difference in basal adenylate cyclase activity between the established DOCA/salt hypertensive and control rats. The adenylate cyclase activities in the established DOCA/salt hypertensive rats were significantly lower with GTP (p less than 0.02) and forskolin (p less than 0.01) as compared with the control rats. Calmodulin elevated the adenylate cyclase activity significantly (p less than 0.05) in the established DOCA/salt hypertensive rats as well as in the control rats. However, enzyme activity with calmodulin in the established DOCA/salt hypertensive rats was significantly lower (p less than 0.05) than that in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Adenylate cyclase activities of vascular smooth muscle in early and established DOCA/salt hypertensive rats. 233 35

Effects of extracellularly applied ATP (added as disodium salt) on stimulus-secretion coupling were investigated in clonal insulin-producing RINm5F cells. Cytoplasmic free Ca2+ concentration [( Ca2+]i), electrical activity, membrane potential, formation of InsP3 and insulin release were measured. Addition of ATP in a Ca2(+)-containing medium promoted a rapid rise in [Ca2+]i, which was followed by a slow decline towards the basal level. In a Ca2(+)-free medium, the ATP-induced increase in [Ca2+]i was smaller, but still enough to elicit insulin secretion. Upon normalization of the extracellular Ca2+ concentration, the response to ATP recovered instantaneously. The presence of glucose in the incubation medium was a prerequisite to obtain a pronounced effect of ATP in the absence of extracellular Ca2+. However, glucose did not enhance the response to ATP in a Ca2(+)-containing medium. The effect of ATP was dose-dependent, with a clearly detectable increase in [Ca2+]i at 1 microM and a maximal response being obtained at 200 microM-ATP. The response to ATP was unaffected by activating adenylate cyclase by forskolin, but was abolished by 10 nM of the phorbol ester phorbol 12-myristate 13-acetate. The effects of ATP on [Ca2+]i could not be accounted for by a generalized increase in plasma-membrane permeability, as evident from the failure of the nucleotide to increase the fluorescence of the nuclear stain ethidium bromide. After stimulation with ATP there was an increase in membrane potential, in both the absence and the presence of extracellular Ca2+. Blockage of the voltage-activated Ca2+ channals with D-600, in a Ca2(+)-containing medium, decreased the effect of ATP on [Ca2+]i slightly. Patch-clamp measurements using the cell-attached patch configuration revealed that the RINm5F cells produce spontaneous action potentials, the frequency of which increased markedly on addition of ATP. Whole-cell recordings demonstrated that the increase in spike frequency was not associated with the development of an inward current, but was rather accountable for by a decrease in the activity of the ATP-regulated K+ channels. Addition of 200 microM-ATP stimulated phospholipase C activity, as evident from the formation of InsP3, both in the absence and in the presence of extracellular Ca2+. Thus in the absence of extracellular Ca2+ the stimulatory effect of ATP on insulin release can be explained by InsP3-induced mobilization of intracellularly bound Ca2+. Hence, in the RINm5F cells extracellular ATP acts in a manner similar to other Ca2(+)-mobilizing agents.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Extracellular ATP increases cytoplasmic free Ca2+ concentration in clonal insulin-producing RINm5F cells. A mechanism involving direct interaction with both release and refilling of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. 240 36

Heparin is known to impair the antiaggregatory effectiveness of prostacyclin (PGI2) for adenosine diphosphate-induced aggregation in citrated platelet rich plasma. Thus porcine mucosal heparin (PMH) from different commercial sources was investigated for its ability to compete with specific platelet prostacyclin binding. In concentrations up to 250 IU/ml PMH itself did not interfere with the binding of 3 X 10(-9) M 9-3H-PGI2-sodium salt to intact washed platelets. The displacement of specifically bound PGI2 observed by PMH (Ki 60 IU/ml) containing 4-chloro-m-cresol (4-CC) was caused by the preservative (Ki 4-CC 3.0 X 10(-4) M). Although 60 IU/ml PMH (free of 4-CC) have been shown to inhibit basal 3 X 10(-5) M forskolin-, and 10(-8)M Iloprost-stimulated adenylate cyclase in platelet membranes (-63%, -62%, -83% respectively), no effect of PMH on 3H-cyclic-AMP formation has been observed when intact platelets were studied by 3H-adenine prelabeling technique. There is also no evidence that the preincubation of PGI2 (5 X 10(-7) M) with 1000 IU/ml PMH might neutralize the effectiveness of this eicosanoid. In contrast, PGI2 preincubated with PMH (10 min, 37 degrees C) caused a more pronounced increase of platelet 3H-cyclic AMP (+65%) compared with PGI2 incubated in 5 X 10(-2) M Tris-HCl, pH 7.4. Thus our data provide no evidence that PMH interferes with i) specific platelet PGI2 binding, ii) PGI2-stimulated cyclic AMP synthesis or iii) neutralizes PGI2 by formation of a biologically less active PGI2-PMH complex.
...
PMID:Effects of heparin on prostacyclin binding and platelet adenylate cyclase activity stimulated by iloprost and forskolin. 243 18

Recently we reported the synthesis of the first enantiomeric pair of irreversible opioid ligands [(3S,4R)-(-)- and (3R,4S)-(+)-cis-4, SUPERFIT] and specific interaction of the latter with the delta receptor. Here we report another enantiomeric pair of irreversible opioid ligands, (+)-trans- and (-)-trans-3-methylfentanyl isothiocyanates [(3S,4S)-(+)-trans- and (3R,4R)-(-)-trans-4]. A single-crystal X-ray analysis of the 2,4,6-trinitrobenzenesulfonic acid salt of (+)-trans-3-methyl-N-phenyl-4-piperidinamine [(+)-trans-8] revealed it (and, therefore, 4) to have the trans configuration and the absolute configuration of (+)-trans-8 to be 3S,4S. The (+)-trans enantiomer of 4 was shown to be highly potent and about 10-fold more selective as an acylating agent than (-)-trans-4 for the higher affinity [3H]DADL (delta) binding site in rat brain membranes. In that assay, (+)-trans-4 and (+)-cis-4 were essentially equipotent as affinity ligands, and the levo enantiomers were considerably less potent. (+)-trans-4 was, thus, a potent, subtype-selective acylating agent for the delta opioid receptor in vitro. With membranes from NG108-15 neuroblastoma x glioma hybrid cells, containing only delta receptors, (+)-cis-4 was found to be a little more potent than (+)-trans-4. Similarly, (+)-cis-4 is the most effective inhibitor of adenylate cyclase in these membranes, (+)-trans-4 has weak activity, and the levo enantiomers are inactive. Only (+)-cis-4 was found to have antinociceptive activity in vivo.
...
PMID:Probes for narcotic receptor mediated phenomena. 15. (3S,4S)-(+)-trans-3-methylfentanyl isothiocyanate, a potent site-directed acylating agent for the delta opioid receptors in vitro. 254 60

Forskolin synergistically potentiated adenosine 3',5'-cyclic monophosphate formation by prostaglandin E1 (PGE1) in rat normal hepatocytes freshly prepared by collagenase digestion and rat ascites hepatoma AH66 cells, but dose-dependently inhibited the accumulation by PGE1 in AH66F cells. Forskolin activated adenylate cyclase in a dose-dependent manner in homogenates of all cell lines. In normal hepatocytes and AH66 cells, simultaneous addition of forskolin and other adenylate cyclase activators [isoproterenol (IPN), PGE1, guanosine 5'-triphosphate sodium salt (GTP), 5'-guanylylimidodiphosphate sodium salt (Gpp (NH)p), NaF, cholera toxin, islet activating protein and MnCl2] gave greater than additive responses. On the other hand, in AH66F cells, the effect of forskolin on adenylate cyclase was hardly influenced by GTP, but forskolin diminished the activities induced by high concentrations of GTP to that by the diterpene alone. Forskolin also significantly inhibited the PGE1-stimulated and the guanine nucleotide binding regulatory protein-stimulated activities. Because AH66F cells were insensitive to IPN, the combination with forskolin and IPN gave similar activity to that obtained with the diterpene alone. The effect of forskolin on the activation by manganese ion was neither synergistic nor inhibitory but was additive in AH66F cells. These results suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide binding regulatory protein and the catalytic unit in normal hepatocytes and AH66 cells, but in AH66F cells forskolin interferes with the coupling of the two components of adenylate cyclase.
...
PMID:Stimulatory and inhibitory effects of forskolin on adenylate cyclase in rat normal hepatocytes and hepatoma cells. 254 54

Sodium regulation of alpha 2-adrenoreceptors was investigated in inbred salt-sensitive (S) and inbred salt-resistant (R) rats fed a high or low salt diet. The systolic blood pressure was higher in S rats than in R rats, and this difference was obviously greater on a high salt diet. In rats fed a low or high salt diet, S rats had higher alpha 2-adrenoreceptor density in the kidneys compared with R rats as measured by [3H]yohimbine binding and Scatchard analysis. The affinity of the receptors in the kidney for the antagonist, yohimbine, was nearly the same in these two strains either on a low or high salt diet. In the brain, the affinities or the numbers of receptors were not significantly different whether these two strains were fed a low or high salt diet. Inclusion of NaCl up to 80 mM in the assay medium did not alter the in vitro binding of [3H]yohimbine in the kidney or brain. On the other hand, inclusion of NaCl in the assay medium reduced the ability of epinephrine in competing with [3H]yohimbine for the receptor sites in the kidney and in the brain, and this effect of NaCl was the same in a given tissue between S and R rats, whether they were fed a low or high salt diet. These results suggest that: (1) in the kidneys, the receptor density and not the receptor affinity was different between S and R strains whether they were fed a low or high salt diet; (2) in the brain, the receptor density and affinity were the same between S and R rats regardless of the diet (low or high salt), indicating that the sodium salt diet modulates the peripheral but not the central alpha 2-adrenoreceptors; and this modulatory effect was observed only in S rats; (3) Na+ was able to reduce the affinity of the agonist (epinephrine) for the receptors in both S and R rats, and this effect of Na+ on central and peripheral alpha 2-adrenoreceptors was similar in prehypertensive rats and rats with salt-induced hypertension; and (4) the resistance of R rats to salt-induced hypertension was not due to the absence of Na+ binding component involved in the regulation of alpha 2-adrenoreceptor-adenylate cyclase complex.
...
PMID:Sodium regulation of alpha 2-adrenoreceptors in Dahl rats. Effect of feeding a low or high salt diet. 255 32

Systolic blood pressure, the affinity and density of the alpha 2-adrenoceptors, Na+ effect on alpha 2-adrenoceptors as measured by specific [3H]yohimbine binding, and Na+ regulation of alpha 2-adrenoceptor-agonist interactions were studied in 6 week and 9 month old inbred salt sensitive (S) and inbred salt-resistant (R) rats. The systolic blood pressure of 6 week old S and R rats was not significantly different, while the systolic blood pressure of 9 month old S rats was higher than the age-matched R rats. The affinity of the alpha 2-adrenoceptors for yohimbine was the same in the 6 week old S and R rats but it was 2-fold less in the 9 month old S rats compared to the age-matched R rats. In the 6 week old rats, the number of alpha 2-adrenoceptors (Bmax) was significantly higher in the S rats than in the R rats; whereas, in the 9 month old rats, the alpha 2-adrenoceptors were 2.6 times higher in the S rats than the age-matched R rats. Na+, up to 80 mM, did not modify the number of alpha 2-adrenoceptors in the 6 week and 9 month old S and R rats. However, Na+ reduced the affinity of the alpha 2-adrenoceptors for epinephrine and this effect of Na+ was found to be the same in the 6 week and 9 month old S and R rats. These findings suggest that Na+ regulation of alpha 2-adrenoceptor-agonist interactions was not altered with age and it was found to be similar in prehypertensive rats and rats with severe hypertension; further, the resistance of R rats to salt-induced hypertension was not due to the absence of Na+ binding component in the alpha 2-adrenoceptor-adenylate cyclase complex.
...
PMID:Sodium regulation of alpha 2-adrenoceptor-agonist interactions in renal membranes of young and old Dahl rats. 256 95

The effects of serotonin receptor agonists and antagonists on the electrically (3 Hz) evoked 3H overflow were determined on pig brain cortex slices preincubated with 3H-serotonin and superfused with physiological salt solution containing indalpine (an inhibitor of serotonin uptake) plus phentolamine. The potencies of the serotonin receptor agonists and antagonists were compared with their affinities for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D binding sites in pig or rat tissue membranes; in addition, the potencies of the agonists were compared to their potencies in inhibiting adenylate cyclase activity in membranes of calf substantia nigra. In the superfusion experiments on pig brain cortex slices the following rank orders of potencies were obtained: agonists, serotonin greater than 5-methoxytryptamine = 5-carboxamidotryptamine greater than RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole) greater than SDZ 21009 (4(3-terbutylamino-2-hydroxypropoxy)indol-2-carbonic-acid-isopr opylester) greater than or equal to yohimbine greater than or equal to cyanopindolol greater than 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) greater than or equal to CGS 12066 B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline); ipsapirone and urapidil were ineffective; antagonists (antagonism determined against 5-methoxytryptamine as an agonist), metitepine greater than metergoline greater than mianserin. Propranolol, spiperone or mesulergine did not produce a shift of the concentration-response curve for 5-methoxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype. 279 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---