Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbenoxolone slightly but significantly decreased the release of FFA from rat epididymal fat pads. The antilipolytic action of carbenoxolone was not blocked by 10(-3)M 3-isobutyl-1-methylxanthine, a potent inhibitor of phosphodiesterase. The findings suggest that carbenoxolone exerts its antilipolytic activity by acting on adenylate cyclase, thereby decreasing cyclic AMP concentrations and the activity of the hormone-sensitive lipase in adipose tissue.
 ...
PMID:Effect of carbenoxolone on lipolysis in rat adipose tissue. 2 44

In open-chest dogs anesthized with sodium pentobarbital, acetylcholine (ACh, 5 times 10'-5M) infused into the left circumflex coronary artery caused an increase in coronary flow and a decrease in myocardial O'2 extraction ratio (P less than .01) anduptake (P less than .05). Heart rate and mean arterial pressure were not altered,although left ventricular dP/dt declined from 2,037 plus or minus 205 to 1,873 plus or minus 194 mmHg/s (P less than .02). Intracoronary administration of norepinephrine (NE, 2.4 times 10'-6M) caused an increase in myocardial O'2 uptake (P less than .02); simultaneous infusion of both NE and ACh caused a decline in O'2 extraction ratio (P less than .01) and uptake (P less than 0.5). Myocardial adenylatecyclase activity in response to ACh was not altered significantly from a control levelof 188 plus or minus 22 pmol of '14C-labeled cyclic AMP/mg protein per 10 min. Norepinephrine alone elevated adenylate cyclase activity to 401 plus or minus 45 pmol ['14C]cyclic AMP/mg protein per 10 min (P less than .01). However, with simultaneous infusion of both NE and ACh, adenylate cyclase returned to control levels. Although ACh alone did not alter myocardial hormone-sensitive lipaseactivity, NE elevated lipolytic activity from 8.1 plus or minus .7 to 13.2 plus or minus 1.8 mueq free fatty acid (FTA)/g per 30 min (P less than .05). The administration of both ACh and NE returned lipase activity to nearly control levels. Myocardial uptake of FFA increased significantly during ACh infusion alone (P less than 0.5) and during NE infusion alone (P less than 905). However, when NE and AChwere administered together, a decline in FFA uptake was observed (P less than .02). These data indicate that the effects of ACh on cardiac metabolism are minimal, withthe decline in myocardial O'2 uptake of ACh primarily reflecting the decrease in contractility. On the other hand, antagonism of ACh on NE-stimulated myocardial lipid metabolism appears to involve activity of the adenylate cyclase system.
 ...
PMID:Acetylcholine and norepinephrine interactions on cardiac lipids and hemodynamics. 115 99

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.
 ...
PMID:Antilipolytic effect of prostaglandin E2 in perifused rat adipocytes. 330 32

Experiments reported here were performed to understand the mechanism by which THF increases the immunocompetence of spleen cells from NTx mice. Dibutyryl cAMP or substances which increase intracellular levels of cAMP in lymphocytes such as Poly(A:U), theophylline, or PGE(2) were shown to mimic the effect of THF and confer reactivity in an in vitro GvH response to spleen cells from NTx mice. Flufenamic acid, an antagonist to PGE(2), was shown to inhibit the induction of competence by this substance. It was found that THF induces competence by activating membranal adenyl cyclase which leads to a rise in intracellular cAMP in thymus-derived cells only. These biochemical changes occur before antigenic stimulation and are unrelated to antigenic challenge. These findings indicate that THF exerts its effect via cAMP and are in agreement with the concepts which permit to classify THF as a thymus hormone.
 ...
PMID:Hormone-like activity of a thymus humoral factor on the induction of immune competence in lymphoid cells. 414 48

Epinephrine, norepinephrine, ACTH, and dibutyryl 3',5'-cyclic AMP reduced adipocyte ATP levels during 60 min incubation; glucose displayed a protective effect. The reduction in adipocyte ATP levels could not be attributed solely to: a direct hormone effect, deficiency in metabolic substrate, activation of adenyl cyclase with ATP consumption, loss of adenine nucleotide from the cell or loss of cells during incubation, lipolytic rate per se, or extracellular accumulation of FFA or glycerol. To determine whether intracellular FFA accumulation was a causative factor, intracellular FFA levels were measured during hormone-stimulated lipolysis. This was accomplished by using sucrose-U-(14)C as a marker for the extracellular space to correct for contamination of cells by extracellular albumin-bound FFA. These experiments showed that the fall in adipocyte ATP correlated with FFA saturation of medium albumin and progressive accumulation of FFA within the adipocyte. Furthermore, the protective effect of glucose noted above was associated with a marked reduction in intracellular FFA as compared to the extracellular FFA pool. On the basis of these studies, combined with those in the literature, it is concluded that in vitro effects of lipolytic agents on adipocyte ATP levels are the net result of imparied ATP synthesis (uncoupled oxidative phosphorylation) in the face of normal or augmented ATP consumption.
 ...
PMID:Reduction in adipocyte ATP by lipolytic agents: relation to intracellular free fatty acid accumulation. 432 9

Adipocyte plasma membranes were isolated from four patients with type 1a pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gs has been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gs activity, and that this blunted response may lead to decreased lipolysis and to obesity.
 ...
PMID:Defective stimulation of adipocyte adenylate cyclase, blunted lipolysis, and obesity in pseudohypoparathyroidism 1a. 806 43

cAMP regulation of gonadotropin secretion and subunit mRNA levels was studied in pituitary cells perifused with pulses of GnRH. Pituitary cells from 7-week-old male rats castrated at 5 weeks of age were stimulated hourly for 9-24 h with 1-min pulses of GnRH, the adenylate cyclase activator forskolin, the cell-permeable cAMP analog 8-bromo-cAMP (8Br-cAMP), or control medium. Cells were also treated with the nonsteroidal antiinflammatory drug flufenamic acid, which reduces pituitary cAMP levels. During perifusion, the effluent was collected in 10-min fractions for FSH and LH assay. At the completion of perifusion, total RNA was extracted, and gonadotropin subunit mRNA levels were quantitated by Northern analysis. Continuous administration of flufenamic acid gradually reduced the amplitude of GnRH-stimulated FSH and LH pulses to nadir values of 40 +/- 4.7% and 62 +/- 12% of the control value, respectively. Flufenamic acid decreased (P < 0.05) FSH beta and alpha-subunit mRNA levels and blocked the effect of GnRH to lengthen LH beta mRNA. Pulses of forskolin or 8Br-cAMP released LH and FSH, and continuous forskolin or 8Br-cAMP potentiated the gonadotropin stimulatory effect of GnRH. Forskolin or 8Br-cAMP increased (P < 0.05) FSH beta mRNA and alpha-subunit mRNA levels when administered in pulses, but not when administered continuously, and lengthened LH beta mRNA. The Nal-Glu GnRH antagonist blocked the effects of GnRH pulses, but not the effects of 8Br-cAMP or forskolin. In conclusion, lowering intracellular cAMP levels with flufenamic acid attenuated GnRH-stimulated gonadotropin secretion, decreased alpha-subunit and FSH beta mRNA levels, and blocked the effect of GnRH to lengthen LH beta mRNA, whereas 8Br-cAMP or forskolin produced the opposite effect. These data extend previous results which suggested that cAMP modulates gonadotropin secretion and indicate that the cAMP/A-kinase pathway regulates each of the gonadotropin subunit mRNAs.
 ...
PMID:Evidence for a role for the cyclic adenosine 3',5'-monophosphate/protein kinase-A pathway in regulation of the gonadotropin subunit messenger ribonucleic acids. 840 51

We previously showed that arachidonic acid and related unsaturated free fatty acids (U-FFAs) inhibit the activity of adenylylcyclase in brain membranes of mice. The level of U-FFAs elevates when the hydrolysis of triacylglycerols (TAGs) and phospholipids is promoted. In this study, we examined whether activation of triacylglycerol lipase (TAG lipase) and phospholipase A(2) (PLA(2)) results in the inhibition of adenylylcyclase activity in cerebellum membranes of mice. Incubation of Intralipos with TAG lipase in the presence of membranes mainly released oleic acid and linoleic acid and caused > or =95% inhibition of adenylylcyclase activity. In contrast, PLA(2), though releasing substantial amounts of U-FFAs, increased the enzymatic activity. To account for this difference, we examined how by-products formed in U-FFA release by TAG lipase and PLA(2) operated on the arachidonic acid-induced inhibition. Lysophosphatidylcholne and some other lysophospholipids, produced by PLA(2), enhanced the adenylylcyclase activity and attenuated the inhibitory effect of arachidonic acid. On the other hand, no such effects were found with by-products of TAG lipase-mediated lipolysis. Rather, monoacylglycerols having U-FFAs, possibly formed by TAG lipase, potentiated the arachidonic acid-induced inhibition of adenylylcyclase. Bovine serum albumin, added into the mixture for the pretreatment of membranes with TAG lipase, prevented the inhibition of adenylylcyclase. These results indicate that by-products formed in U-FFA release have a crucial role for the U-FFA's action on adenylylcyclase and that U-FFAs released from TAG are an inhibitor of adenylylcyclase. It may be that albumin in plasma, and thus FFA-binding proteins within cells, are of importance in protecting adenylylcyclase upon U-FFA release.
 ...
PMID:Inhibition of adenylylcyclase activity in mouse cerebellum membranes upon hydrolysis of triacylglycerols by triacylglycerol lipase, but not phospholipids by phospholipase A(2). 1151 69