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)

Cardiac myosin heavy chain expression undergoes a perinatal transition from predominance of beta-MHC to alpha-MHC. In the current study, we tested the effects of glucocorticoids in this early transition period, by treating pregnant rats with dexamethasone on gestational days 17, 18 and 19, using doses below (0.05 mg/kg), at (0.2 mg/kg) or above (0.8 mg/kg) the threshold for growth retardation. Cardiac MHC isoforms were resolved with a denaturing SDS-PAGE system, followed by quantitative densitometry. In normal animals alpha-MHC was only 10% of the total on gestational day 18 but rose to 35% by postnatal day 1, and to 95% by the end of the first month postpartum. During the early phase of this transition, the lowest dose of dexamethasone significantly promoted alpha-MHC expression without inhibiting body or heart growth; regression analysis indicated a 40% increase in the slope of MHC isoform transition with respect to tissue weight. In contrast, the higher, growth-retarding doses of dexamethasone either failed to enhance alpha-MHC expression or caused biphasic changes, with inhibition at ages corresponding to the onset of weight deficits; regression analysis indicated that the effects of the higher doses on MHC could all be accounted for by changes in tissue weight. Glucocorticoid levels rise substantially in the period surrounding parturition, and serve to program the development and coupling of adenylate cyclase to membrane receptors; because adenylate cyclase has been shown to elicit the beta-MHC to alpha-MHC transition in vitro, our results suggest that glucocorticoids, along with thyroid hormone and beta-adrenergic stimulation, influence the ontogenetic program of MHC isoform transition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoids accelerate the ontogenetic transition of cardiac ventricular myosin heavy-chain isoform expression in the rat: promotion by prenatal exposure to a low dose of dexamethasone. 128 77

Cardiac myosin heavy chain (MHC) expression undergoes an ontogenetic transition from beta to alpha MHC isoforms. Although thyroid hormone plays a role in this change, the timing of the events suggests the participation of other factors. Using a new, denaturing SDS-PAGE procedure that cleanly resolves the beta and alpha heavy chains, we have assessed the role of beta-adrenergic stimulation on this transition in fetal and neonatal rat hearts. In control animals at embryonic day 20, less than 15% of the MHC was the alpha-form, and the proportion increased to approximately 35% by postnatal day 1 and to 80% by postnatal day 8. Although catecholamine levels rise abruptly at birth, and cyclic AMP levels increase the expression of alpha-MHC in vitro, neither premature beta-adrenergic stimulation (maternal treatment with terbutaline on embryonic days 17, 18 and 19) nor continuous prenatal blockade of beta-receptors (maternal propranolol infusions from embryonic day 7 onward) influenced the developmental profile. Because beta-receptors in fetal and neonatal heart are functionally linked to adenylate cyclase, and cyclic AMP has been shown to promote the expression of alpha-MHC, the lack of effect of terbutaline or propranolol suggests that activation of adenylate cyclase through fetal cardiac beta-receptors is not sufficient to mediate the switchover without participation of other factors, such as thyroid or steroid hormones, or hypoxia.
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PMID:Ontogenetic transition of cardiac myosin heavy chain isoforms in rat ventricle: effects of fetal exposure to beta-adrenergic agonists or antagonists. 135 26

Cyclic AMP stimulation of chemotactically competent Dictyostelium amebas labeled with [32P]orthophosphate transiently increases phosphorylation in the heavy chain and the 18,000 dalton light chain of myosin. Immediately before the increase, heavy chain phosphorylation transiently decreases. These phosphorylation changes also occur when cAMP-induced activation of adenylate cyclase is blocked by pretreatment of amebas with caffeine. The time course of these phosphorylation responses correlates with the shape changes induced in amebas exposed to a temporal increase in cAMP concentration. The dose dependence of the phosphorylation responses is the same as that previously determined for chemotaxis. The phosphorylation responses exhibit adaptation properties in common with those of the shape change response and chemotaxis. Increases in the rate of myosin heavy chain and light chain phosphorylation can be observed in vitro by stimulating unlabeled amebas with cAMP and then lysing the cells into a gamma-[32P]ATP-containing reaction mixture.
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PMID:Chemoattractant-elicited increases in myosin phosphorylation in Dictyostelium. 300 Jun 4

In primary cultures of chick 11-day embryonic tissue a number of phosphodiesterase inhibitors were found to elevate acetylcholine receptor levels. Of these agents, Ro20-1724 was the most effective, elevating surface receptor content by 2-fold after 48 h of treatment. 8-Br-cAMP and cholera toxin, a natural activator of adenylate cyclase, mimicked the effect of Ro20-1724, while 8-Br-cGMP and dibutyryl cGMP had no effect. Cholera toxin, 8-Br-cAMP, and Ro20-1724 all increased the insertion rate of new receptor into the surface membrane without altering degradation. The enhanced insertion appears related to an actual increase in synthesis since total acetylcholine receptor was elevated by exposure to cholera toxin. In contrast, no change in creatine phosphokinase activity, myosin heavy chain content, or [35S] methionine incorporation into total cellular protein was observed during cholera toxin treatment. These results suggest that cAMP plays a role in the regulation of acetylcholine receptor.
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PMID:Regulation of acetylcholine receptor by cyclic AMP. 624 32

Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.
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PMID:Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy. 839 91