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)

Chymotryptic activation of adenylate cyclase from rat heart was examined with respect to guanosine triphosphate (GTP), adenosine triphosphate (ATP) and Mg2+ concentrations. The activation was inhibited by aprotinin. In the absence or presence of GTP, chymotrypsin stimulated the cyclase at the same ratio. GTP exerted stimulatory (up to 0.1 mM) and inhibitory (at 1 mM) effects on the cyclase. Both effects were not affected by chymotrypsin. ATP at low concentrations increased the cyclase activity dose dependently and at high concentrations decreased the cyclase activity. Chymotrypsin retarded the appearance of the decreasing phase. This effect of chymotrypsin was similar to that of increasing the concentration of Mg2+ in the reaction mixture. According to double-reciprocal plots of Mg2+ concentrations and the cyclase activity, chymotrypsin diminished Km for Mg2+ with little effect on the Vmax. Hill plots of the same data showed that the Hill coefficient was about 1 and was not altered by chymotrypsin. These results suggest that chymotryptic activation of adenylate cyclase is mainly due to increasing the affinity for Mg2+ of the system.
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PMID:Increase in Mg2+ affinity as a possible mechanism of chymotryptic activation of adenylate cyclase in rat heart membranes. 241 40

The authors report the effects of four proteases (trypsin, plasmin, chymotrypsin and thrombin) on human heart adenylate cyclase (HHAC) activity. Trypsin and plasmin inhibited HHAC at concentrations higher than 0.3 and 1 microgram/ml, respectively. Chymotrypsin had a biphasic effect, with a stimulation (from 0.5 to 10 micrograms/ml) followed by an inhibition at higher concentrations. Maximal stimulation was obtained at 3 micrograms/ml and averaged 67.2 +/- 5.4%. Thrombin had no significant effect at concentrations up to 1 mg/ml. These data indicate that proteases might regulate HHAC and therefore influence cardiac function.
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PMID:The effects of trypsin, plasmin, chymotrypsin and thrombin on human heart adenylate cyclase activity. 295 13

We previously reported the activation of adenylate cyclases from rat brain (Johnson, R. A., Awad, J. A., Jakobs, K. H., and Schultz, G., (1983) FEBS Lett. 152, 11-16) and from human platelets (Jakobs, K. H., Johnson, R. A., and Schultz, G. (1983) Biochim. Biophys. Acta 756, 369-375) by a factor derived from bovine sperm. In this report we describe the conditions for the extraction of the factor from bovine sperm and characteristics of its effects on adenylate cyclase which are consistent with its being a protease. The activating capacity of sperm particles was extracted from previously washed and frozen sperm into a 30,000 X g supernatant fraction by various salts, but not by the nonionic detergent Lubrol-PX. The amount of extracted factor: (a) was greatest with NH4HCO3 greater than NaCl greater than Na acetate; (b) was optimal with 0.5 M salt; (c) was not appreciably affected by the pH of the extraction buffer between pH 5.0 and 8.5; and (d) exhibited the greatest specific activity at the lower pH. The extracted sperm factor could be concentrated without loss by ultrafiltration on Amicon PM-10 membranes. The effect on adenylate cyclase of concentrated and desalted sperm extracted was inhibited 50% by various salts at 10 to 30 mM. The effects of the sperm factor to activate platelet adenylate cyclase, to block its inhibition via the alpha-adrenoceptor, and to block inhibition of stimulated forms of the enzyme by stable guanine nucleotides were prevented by protease inhibitors. A 50% reduction in the sperm factor's activation of platelet adenylate cyclase was caused by 30 nM soybean trypsin inhibitor, 30 nM alpha 2-macroglobulin, 300 nM leupeptin, 1 microM antipain, 15 microM aprotinin, and 100 microM benzamidine. Up to 3 mM phenylmethanesulfonyl fluoride was without effect on activation of the platelet cyclase by the sperm factor. The effects of the sperm factor persisted after its removal by the washing of pretreated platelet membranes and after its inactivation by the subsequent addition of leupeptin. The data strongly support the conclusion that the bovine sperm factor is a trypsin-like protease. alpha-Chymotrypsin, trypsin, and sperm acrosin were comparably effective in stimulating the platelet adenylate cyclase 5- to 8-fold, with concentrations eliciting maximal stimulation being: 200 ng trypsin/ml; 2 micrograms alpha-chymotrypsin/ml; and 2 micrograms acrosin/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Extraction of the adenylate cyclase-activating factor of bovine sperm and its identification as a trypsin-like protease. 388 Jul 36

Treatment of intact pigeon erythrocytes with trypsin or alpha-chymotrypsin does not alter the isoproterenol-dependent adenylate cyclase activity in plasma membranes prepared after proteolysis. However, both proteases affect adenylate cyclase activity when isolated membranes are digested. Thus, the proteases probably act at the cytoplasmic side of the membranes. This conclusion is supported by the finding that proteases are able to inhibit NADH cytochrome c oxidoreductase, an enzyme located on the inner face of the plasma membrane. In isolated membranes, trypsin inhibits adenylate cyclase. Chymotrypsin (2.5 microgram/ml, 10 min, 37 degrees C) activates adenylate cyclase about 3-fold when the enzyme activity is measured with NaF, guanosine 5'-(beta, gamma-imino)-triphosphate, or guanosine 5'-(beta, gamma-imino)-triphosphate and isoproterenol. Chymotrypsin also activates adenylate cyclase in membranes pretreated with cholera toxin. Activation by chymotrypsin is not expressed when adenylate cyclase is assayed with 5 mM Mn2+ without guanine nucleotides or fluoride. However, the chymotryptic activation is expressed when guanosine 5'-(beta, gamma-imino)-triphosphate is present together with Mn2+. We conclude that interaction of the guanine nucleotide regulatory subunit with the catalytic subunit of adenylate cyclase is required for expression of chymotryptic activation.
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PMID:The site of alpha-chymotryptic activation of pigeon erythrocyte adenylate cyclase. 737 11

The effects of pituitary adenylate cyclase-activating peptide (PACAP-38) and vasoactive intestinal polypeptide (VIP) were investigated in the gastric fundus strips of the mouse. In carbachol (CCh) precontracted strips, in the presence of guanethidine, electrical field stimulation (EFS) elicited a fast inhibitory response that may be followed, at the highest stimulation frequencies employed, by a sustained relaxation. The fast response was abolished by the nitric oxide (NO) synthesis inhibitor L-N(G)-nitro arginine (L-NNA) or by the guanylate cyclase inhibitor (ODQ), the sustained one by alpha-chymotrypsin. alpha-Chymotrypsin also increased the amplitude of the EFS-induced fast relaxation. PACAP-38 and VIP caused tetrodotoxin-insensitive sustained relaxant responses that were both abolished by alpha-chymotrypsin. Apamin did not influence relaxant responses to EFS nor relaxation to both peptides. PACAP 6-38 abolished EFS-induced sustained relaxations, increased the amplitude of the fast ones and antagonized the smooth muscle relaxation to both PACAP-38 and VIP. VIP 10-28 and [D-p-Cl-Phe6,Leu17]-VIP did not influence the amplitude of both the fast or the sustained response to EFS nor influenced the relaxation to VIP and PACAP-38. The results indicate that in strips from mouse gastric fundus peptides, other than being responsible for EFS-induced sustained relaxation, also exerts a modulatory action on the release of the neurotransmitter responsible for the fast relaxant response, that appears to be NO.
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PMID:Modulation of nitrergic relaxant responses by peptides in the mouse gastric fundus. 1117 75

We examined the characteristics of the non-adrenergic non-cholinergic (NANC) nerve induced relaxation and the possible interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) on the basal tone of the circular muscle of the rat gastric fundus. Electrically induced NANC relaxations were partly inhibited by N(omega)-nitro-L-arginine (100 microM), whereas sodium nitroprusside (SNP; 10 microM) and VIP (5 nM) induced relaxations were not affected. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; 5 microM) also inhibited the responses to electrical stimuli to a similar extent as N(omega)-nitro-L-arginine but not VIP. However, AMT plus N(omega)-nitro-L-arginine did not give an additional inhibition above that of each drug alone on NANC relaxations, and dexamethasone (10 microM) had no effect on NANC nerve induced relaxations. 1H-[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM), a selective inhibitor of guanylate cyclase, abolished the responses to NANC nerve stimulation and SNP, while VIP responses were not influenced. N-ethylmaleimide (100 microM), an adenylate cyclase inhibitor, attenuated relaxations to NANC nerve stimulation, VIP and isoproterenol (1 nM), while having no effect on those to SNP, but in combination with N(omega)-nitro-L-arginine, there was no additional inhibition on the responses to nerve stimulation. Alpha-chymotrypsin (10 u ml(-1)) severely diminished VIP induced relaxations, but did not reduce electrical responses. In conclusion, these results suggest that NO is involved in the relaxations induced by short-term electrical stimulation. However, another possible unidentified transmitter that can trigger the accumulation of cyclic GMP is not entirely ruled out and there is no interaction between NO and VIP in the circular muscle strip of the rat gastric fundus, even in the basal state of the tissue.
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PMID:Involvement of nitric oxide in non-adrenergic non-cholinergic relaxation and action of vasoactive intestinal polypeptide in circular muscle strips of the rat gastric fundus. 1152 89

Adenylate cyclase in synaptic plasma membranes from rat brain is activated by ?-chymotrypsin or trypsin. These proteases also activate adenylate cyclase reconstituted from the catalytic subunit of adenylate cyclase and the partially purified fraction of the GTP-binding proteins containing both the stimulatory and inhibitory GTP-binding proteins. Properties of the activation of reconstituted adenylate cyclase by the proteases are as follows. (1) The proteases do not directly activate the catalytic subunit. However, the pre-treatment of the partially purified GTP-binding proteins with ?-chymotrypsin (100 ?g/ml) increases the subsequently reconstituted cyclase activity at least 3-fold. Trypsin (10-30 ?g/ml) much more weakly enhances the cyclase activity. (2) ?-Chymotrypsin and trypsin synergistically activate the cyclase. (3) Trypsin but not ?-chymotrypsin no longer activates the cyclase when the purified stimulatory GTP-binding protein (Gs) replaces the partially purified GTP-binding proteins. (4) The stimulatory effects of ?-chymotrypsin and trypsin on the cyclase activity are little or slight unless 5?-guanylylimidodiphosphate (Gpp(NH)p) is present in the reconstitution. (5) The purified ??-subunits of the GTP-binding proteins markedly inhibit adenylate cyclase. This inhibition is nearly completely attenuated by treating the ??-subunits with ?-chymotrypsin (> 10 ?g/ml). (6) Trypsin (1-10 ?g/ml) inactivates the GTPase of the ?-subunit of the inhibitory GTP-binding protein (Gi). This inactivation of the GTPase seems to correlate with the activation of the reconstituted adenylate cyclase by trypsin. We conclude that two distinct protein components are involved in the activation of adenylate cyclase by ?-chymotrypsin and trypsin. One component sensitive to ?-chymotrypsin is probably the ??-subunits of the GTP-binding proteins. The other component sensitive to trypsin may be the ?-subunit of Gi.
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PMID:Activation of rat brain adenylate cyclase by proteases: involvement of distinct protein components in the activation by ?-chymotrypsin and trypsin. 2050 Dec 51