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)

The major phenobarbital-inducible cytochrome P-450 purified from rat liver, a member of family II of the cytochrome P-450 gene superfamily, is rapidly phosphorylated by cAMP-dependent protein kinase. The phosphorylation reaches greater than 0.5 mol phosphate/mol P-450 after 5 min and is accompanied by a decrease in enzyme activity. The serine residue in position 128 was shown to be the sole phosphorylation site and a conformational change of the protein was indicated by a shift of the carbon monoxide difference spectrum of the reduced cytochrome from 450 to 420 nm. Comparison of amino acid sequences of various cytochrome P-450 families revealed a highly conserved arginine residue in the immediate vicinity of the phosphorylated serine residue which constitutes the kinase recognition sequence. It also revealed that only the members of the cytochrome P-450 family II carry this kinase recognition sequence. To find out whether this phosphorylation also occurs in vivo, the exchangeable phosphate pool of intact hepatocytes derived from phenobarbital-pretreated rats was labeled with 32Pi followed by an incubation of the cells with the membrane-permeating dibutyryl-cAMP or with the adenylate cyclase stimulator glucagon to activate endogenous kinase. As a result, a microsomal polypeptide with the same electrophoretic mobility as cytochrome P-450 became strongly labeled. Peptide mapping and immunoprecipitation with monospecific antibodies identified this protein as the major phenobarbital-inducible cytochrome P-450. It becomes phosphorylated at the same serine residues as in the cell-free phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphorylation of hepatic phenobarbital-inducible cytochrome P-450. 258 91

A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues. Its amino acid sequence was revealed as: His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln- Met-Ala- Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys - NH2. The N-terminal sequence shows 68% homology with vasoactive intestinal polypeptide (VIP) but its adenylate cyclase stimulating activity was at least 1000 times greater than that of VIP. It increased release of growth hormone (GH), prolactin (PRL), corticotropin (ACTH) and luteinizing hormone (LH) from superfused rat pituitary cells at as small a dose as 10(-10)M (GH, PRL, ACTH) or 10(-9)M (LH). Whether these hypophysiotropic effects are the primary actions of the peptide or what physiological action in the pituitary is linked with the stimulation of adenylate cyclase by this peptide remains to be determined.
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PMID:Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. 280 20

A photoreactive analogue of vasopressin, [1-(3-mercapto)propionic acid, 8-(N6-4-azidophenylamidino)lysine]-vasopressin, was compared to salmon calcitonin and [8-arginine]-vasopressin with respect to stimulation of cAMP synthesis in the LLC-PK1 pig kidney epithelial cell line. Without photoactivation, the vasopressin analogue-elicited responses were identical to those induced by vasopressin, in that cAMP synthesis returned to the basal, unstimulated level about 4 h after hormonal treatment. In contrast, the levels of activation of cAMP-dependent protein kinase induced by salmon calcitonin returned to basal approx. 12 h after hormone addition. When activated by ultraviolet irradiation, the vasopressin analogue induced 'permanent' stimulation of adenylate cyclase, whereby cAMP production could be detected even 12.5 h after treatment. Both salmon calcitonin and the photoactivated vasopressin analogue inhibited growth of LLC-PK1 cells, in contrast to vasopressin or the nonactivated analogue. Growth inhibition appeared to be a consequence of the prolonged stimulation of adenylate cyclase. This conclusion was supported by the fact that a LLC-PK1 cell mutant in cAMP-dependent protein kinase was resistant to growth inhibition by salmon calcitonin and activated vasopressin analogue. The results imply that the cAMP-dependent protein kinase is the mediator of the hormone-stimulated growth inhibition.
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PMID:Long-term stimulation of cAMP production in LLC-PK1 pig kidney epithelial cells by salmon calcitonin or a photoactivatable analogue of vasopressin. 282 May 5

The "antigonadal" potential of the neurohypophysial hormones, previously demonstrated in vitro, was evaluated in vivo using hypophysectomized male rats. This approach minimizes the likelihood that the in vivo "antigonadal" effect of the neurohypophysial hormones may be due to their ability to attenuate the release of pituitary gonadotropins. Given that the identity of the putative endogenous occupant of testicular pressor-selective neurohypophysial receptors remains uncertain, use was made of a substitute probe, arginine vasotocin (AVT), the utility of which has been demonstrated in vitro. Concurrent in vivo treatment of follicle-stimulating hormone (FSH; 5 micrograms/rat/day)-maintained immature hypophysectomized rats with increasing doses of AVT (0.25-25 microgram/rat/day) produced significant (P less than 0.05) dose-dependent inhibition of the testicular luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor binding capacity (but not affinity; Kd = 1.8 X 10(-10) M) from 8.8 +/- (standard error; SE) 0.4 ng/testis to a level (3.2 +/- 0.2 ng/testis) lower than that of controls (64% reduction). This AVT-induced decrease in the testicular LH/hCG receptor content of FSH-maintained immature hypophysectomized rats was associated with significant (P less than 0.05) decrements in the hCG- and N6, 2'-O-dibutyryladeosine cyclic 3',5'-monophosphate [( Bu]2cAMP)-stimulated accumulation of 3 alpha-hydroxy-5 alpha-androstan-17-one (androsterone; 52% and 42% inhibition, respectively), with virtual elimination (98% inhibition) of the forskolin-stimulated accumulation of extracellular cAMP by testicular incubates in vitro, as well as with profound suppression of spermatogenesis. Taken together, these observations indicate that the "antigonadal" effect of the neurohypophysial hormones previously demonstrated in vitro, can be fully reproduced in vivo, and that the "antigonadal" activity of the neurohypophysial hormones may be accounted for, in large part, by decreased testicular LH/hCG binding capacity, stimulable adenylate cyclase activity, and cAMP-supported androgen biosynthesis.
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PMID:Antigonadal activity of the neurohypophysial hormones: in vivo regulation of testicular function of hypophysectomized rats. 282 23

The stimulatory GTP-binding protein (Gs) of the uncoupled mutant of S49 lymphoma cells is deficient in its ability to transduce hormonal signals from ligand-bound beta-adrenergic receptors to the catalytic component of adenylate cyclase. In order to define the genetic defect in the Gs of uncoupled S49 cells, a complementary DNA clone encoding the alpha-subunit of Gs was analyzed and the deduced primary structure of the defective subunit compared to that of the wild-type subunit. A single nucleotide transversion was found that coded for a proline rather than an arginine at residue 389. The results indicate a domain of the alpha-subunit of Gs that specifically interacts with hormone receptors.
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PMID:Identification of the lesion in the stimulatory GTP-binding protein of the uncoupled S49 lymphoma. 282 31

This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3-10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 micrograms/min) and glucose disappearance rates were reduced (P less than 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.
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PMID:Theophylline prevents the inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion in man. 283 98

An analog of salmon calcitonin (sCT) has been synthesized, substituting Arg at positions 11 and 18 and Lys at position 14 to provide a free amino group for derivatization. The potency of [Arg11,18,Lys14]sCT was equivalent to that of sCT in activating adenylate cyclase in UMR 106-06 cells. The analog was derivatized with biotin, fluorescein, or 4-azidobenzoate without loss of activity. The derivatized analog was not degraded by lysine-specific endoprotease, whereas the underivatized [Arg11,18,Lys14]sCT was cleaved at Lys-14. The derivatized analogs were purified by HPLC and subsequently shown to possess full biological activity. The photoactive analog was used to photolabel 88,000 and 71,000 mol wt components of the calcitonin receptor in rat osteoclasts, but only an 88,000 mol wt component was photolabeled in the UMR 106-06 cells.
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PMID:Biologically active, derivatizable salmon calcitonin analog: design, synthesis, and applications. 284 Oct 96

The role of guanine nucleotide-binding proteins (G proteins) in the cAMP-dependent action of serotonin (5-HT) and the antagonistic action of the neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF-amide), mediated by the lipoxygenase metabolites of arachidonic acid, was investigated in Aplysia sensory neurons. Intracellular injection of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) mimics the hyperpolarizing action of FMRF-amide due to activation of the S K+ current and alters the transient response to FMRF-amide into an irreversible (or only partially reversible) response. At higher concentrations, GTP[gamma-S] occludes the response to FMRF-amide. Injection of activated pertussis toxin inhibits the response to FMRF-amide but not to 5-HT. Injection of guanosine 5'-[beta-thio]diphosphate inhibits the response to FMRF-amide by approximately equal to 50% and completely blocks the response to 5-HT. Three lines of evidence suggest that the FMRF-amide-activated G protein is involved at an early stage of the arachidonic acid cascade, prior to the release of arachidonate. (i) Pertussis toxin injection blocks the hyperpolarizing response to FMRF-amide but not to exogenously applied arachidonic acid. (ii) Two blockers of the arachidonic acid cascade inhibit the hyperpolarizing responses to both FMRF-amide and GTP[gamma-S] (and unmask a 5-HT-like depolarizing response to the nucleotide). (iii) Concentrations of GTP[gamma-S] that alter the kinetics of the FMRF-amide response have no effect on the hyperpolarizing response to arachidonic acid. We conclude that a pertussis toxin-sensitive G protein most likely acts to couple the FMRF-amide receptor to phospholipase activation and arachidonic acid release, whereas a pertussis toxin-insensitive G protein couples the 5-HT receptor to adenylate cyclase.
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PMID:Role of two different guanine nucleotide-binding proteins in the antagonistic modulation of the S-type K+ channel by cAMP and arachidonic acid metabolites in Aplysia sensory neurons. 284 23

Pretreatment of A-10 cells with pertussis toxin had no effect on [arginine]vasopressin-mediated inhibition of cyclic nucleotide accumulation. Pretreatment of the cells with the same concentration of pertussis toxin produced 90-95% inhibition of [32P]ADP ribosylation in membranes, suggesting that these cells possess pertussis-toxin substrate and that the toxin enters the cells to reach its site of action. The functional integrity of the pertussis-toxin substrate in these cells is confirmed by the observation that in these cell membranes increasing concentrations of GTP inhibited basal, forskolin- and NaF-stimulated adenylate cyclase activities, and this inhibition was abolished when the cells were pretreated with pertussis toxin. In addition, thrombin-mediated inhibition of isoprenaline-stimulated cyclic AMP accumulation was also inhibited by pertussis-toxin pretreatment of the cells. These data suggest that, unlike thrombin, [arginine]vasopressin-induced inhibitory effects on cyclic nucleotide accumulation in smooth-muscle cells are not mediated by pertussis-toxin substrate.
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PMID:Inhibition of formation of cyclic AMP and cyclic GMP by vasopressin in smooth-muscle cells is insensitive to pertussis toxin. 284 52

The effects of serotonin (5-HT), dopamine (DA), several peptides including FMRFamide and arginine vasotocin, the diterpene forskolin and Ca2+ were examined on adenylate cyclase in a particulate fraction from hearts of Aplysia californica. Enzyme activity was stimulated 6-7-fold by 5-HT (EC50, 1 microM) in the presence of GTP. Several 5-HT analogs particularly 5-methoxytryptamine and 5-methoxy-N-N-dimethyltryptamine were also active. The stimulatory action of 5-HT was antagonized by the 5-HT receptor blockers methergoline and metitepine and by the DA receptor blocker chlorpromazine. Dopamine had weak stimulatory action (EC50, 10 microM) and an efficacy relative to that of 5-HT of 0.3. The action of DA was antagonized by chloropromazine and metitepine. Several peptides including FMRFamide and arginine vasotocin had no effect on adenylate cyclase when tested over the concentration range 0.1-100 microM. The enzyme was stimulated 6-fold by the diterpene forskolin (EC50, 2 microM). 5-HT-stimulated activity was strongly inhibited by Ca2+. Calmodulin had no action on the enzyme in the presence of Ca2+.
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PMID:Stimulation of adenylate cyclase in the heart of Aplysia californica by biogenic amines. 285 32


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