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)

Platelet-activating factor (PAF) is not only a potent proinflammatory compound, but is also involved in cell proliferation and differentiation. cDNAs coding for PAF receptors were isolated in our laboratory from human, guinea-pig, rat, and mouse. They consist of 341-342 amino acids with 7 putative transmembrane domains, characteristic of a G-protein-coupled-receptor superfamily. The gene for the human PAF receptor is located on chromosome 1, and has three separate exons. By 5'-alternative splicing, two transcripts (leukocyte- and heart-type) were expressed under the direction of two distinct promoters. Signal transduction of the PAF receptor disclosed that it couples with many effector systems including phospholipase C activation, inhibition of adenylate cyclase, MAP kinase activation, and phospholipase A2 activation. The multiplicify of these second messenger systems allows PAF to have a variety of biological activities, even though it is a single molecule and has no receptor subtypes.
...
PMID:[Platelet-activating factor-from molecular biology to clinic]. 760 49

Bradykinin receptors have been identified in human gingival fibroblasts; the primary signal transduction pathways and their dependence on calcium have been characterized. Binding data revealed a calcium-independent binding of bradykinin to the cell membrane with a receptor density of 25,000 receptors per cell and a Kd of 1.6 nM. The bradykinin receptor-mediated activation of phospholipase C (PLC) resulted in an extensive and rapid stimulation of phosphoinositide metabolism. Using radioreceptor assay techniques, in the absence of LiCl, the inositol 1,4,5-trisphosphate (Ins 1,4,5P3) generation was found to be transient, with maximal levels attained within 15 s. An EC50 of 12 nM was observed for the accumulation of total inositol polyphosphates. The activation of phospholipase A2 (PLA2), and the subsequent release of arachidonic acid and the primary metabolite prostaglandin E2, also was found to be time- and concentration-dependent. Stimulation of tyrosine kinase activity by bradykinin was concentration-dependent and resulted in the phosphorylation of three substrates of unknown identity. Bradykinin stimulation did not activate adenylate cyclase as there occurred no increase in the generation of cyclic AMP. The mobilization of intracellular calcium stores followed closely the Ins 1,4,5 P3 kinetics and had an EC50 of 11 nM. Chelation of extracellular calcium reduced significantly the duration of the calcium response, while only minimally lowering the rapid, maximal increase in intracellular free calcium concentration ([Ca2+]i). A sustained elevation of [Ca2+]i was found to be essential in PLC and PLA2 signaling, as well as in tyrosine kinase activation, suggesting a major role for membrane calcium channels in bradykinin stimulation of cellular responses in these cells. Bradykinin was found to inhibit dramatically epidermal growth factor-induced DNA synthesis in confluent cells, although to a much lesser degree in subconfluent cells. This pattern was similar to the observed maximal specific increase in bradykinin binding with confluency. Together these results demonstrate the presence of bradykinin receptors in human gingival fibroblasts; these receptors are coupled to signal transduction mechanisms involving the PLC, PLA2, and tyrosine kinase effector systems, all of which require extracellular calcium to achieve maximal activation.
...
PMID:Bradykinin receptors and signal transduction pathways in human fibroblasts: integral role for extracellular calcium. 768 36

Mesenchymal cells are continually stimulated by a wide spectrum of biological mediators. These mediators bind to receptors on the cell surface and initiate a cascade of signaling events. The initial signal transduction pathways known to be stimulated in mesenchymal cells included phospholipase C, phospholipase D, phospholipase A2, adenylate cyclase, receptor tyrosine kinases, and receptor serine/threonine kinases. These pathways are reviewed and specific applications for therapeutic intervention in wound healing and regenerative therapy in the periodontium are discussed.
...
PMID:Signal transduction mechanisms in mesenchymal cells. 770 25

Renal mesangial cells express group II phospholipase A2 in response to two principal classes of activating signals that may interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) and agents that elevate cellular levels of cAMP such as forskolin, an activator of adenylate cyclase. Using pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor NF kappa B, we determined its role in cytokine--and cAMP--triggered group II PLA2 expression. Micromolar amounts of PDTC suppress the IL-1 beta- and TNF alpha-dependent, but not the forskolin-stimulated group II PLA2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of group II PLA2 mRNA steady state levels in response to IL-1 beta and TNF alpha, while only marginally affecting forskolin-induced PLA2 mRNA levels. Our data suggest that NF kappa B activation is an essential component of the cytokine signalling pathway responsible for group II PLA2 gene regulation and that cAMP triggers a separate signalling cascade not involving NF kappa B. These observations may provide a basis to study the underlying mechanisms involved in the regulation of group II PLA2 gene expression.
...
PMID:Pyrrolidine dithiocarbamate differentially affects cytokine- and cAMP-induced expression of group II phospholipase A2 in rat renal mesangial cells. 775 May 75

Muscarinic receptors regulate a number of important basic physiologic functions including heart rate and motor and sensory control as well as more complex behaviors including arousal, memory, and learning. Loss of muscarinic receptor number or function has been implicated in the etiology of several neurological disorders including Alzheimer's dementia, Down's syndrome, and Parkinson's disease. Muscarinic receptors transduce their signals by coupling with G-proteins, which then modulate the activity of a number of effector enzymes and ion channels. Five subtypes of muscarinic receptors (m1-m5) have been identified by molecular cloning and much has been learned about their distribution, pharmacology, and structure. Less is known about the molecular mechanisms of receptor-effector coupling and the biological role of each receptor subtype. The ectopic expression of genes encoding a single muscarinic receptor subtype in mammalian cell lines has provided an important model system in which to investigate receptor subtype-specific pharmacology and signal transduction. Expression models have revealed that single muscarinic receptor m1, m3, or m5 subtypes can activate multiple signaling effectors simultaneously including phospholipases A2, C, and D, as well as tyrosine kinase and a novel class of voltage-insensitive calcium channels. The m2 or m4 receptors have been shown to augment phospholipase A2 in addition to their established role as inhibitory receptors acting through the attenuation of adenylate cyclase. In addition to allowing investigations of the regulatory mechanisms of muscarinic receptors, expression models provide an excellent tool to investigate receptor-subtype specific physiology and pharmacology.
...
PMID:Muscarinic acetylcholine receptors: signal transduction through multiple effectors. 776 53

The technique of fluorescence recovery after photobleaching was used to measure the lateral mobility of membrane integral proteins in reticulocyte plasma membranes which were treated to modify the 'fluid' lipid or immobilized protein fractions, hence increasing the relative prevalence of obstacles to protein lateral motion. This was achieved by either: (1) treating the plasma membranes with phospholipase A2 followed by extraction of the hydrolysis products using fatty-acid-free bovine serum albumin, resulting in a decrease in the membrane 'fluid' lipid portion; or (2) preincubating the plasma membranes with polylysines, resulting in plasma membrane protein aggregation and immobilization. As the prevalence of obstacles to lateral motion increased in plasma membranes through the treatments described above, the mobility of the membrane integral proteins diminished. Experimental results for the dependence of protein mobility on the prevalence of obstacles to lateral motion were compared to theoretical data in order to verify the applicability of the percolation theory to reticulocyte plasma membranes. The influence of a decrease in the 'fluid' lipid and an increase in the immobilized membrane protein fractions upon the hormone-stimulated adenylate cyclase activity has been studied as well. As the 'solid' lipid and immobilized membrane protein fractions decreased, both the hormone-stimulated adenylate cyclase activity and the fraction of beta-adrenergic receptors with high affinity to hormone diminished. It was shown that this correlation can be caused by a decrease in membrane fraction accessible to the movement of the interacting proteins of the adenylate cyclase complex. Hormonal stimulation of adenylate cyclase is discussed in terms of the percolation theory.
...
PMID:Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory. 779 48

The regulation of corticosteroid secretion of the adrenal cortex (interrenal tissue) of axolotl (Ambystoma mexicanum) was studied using in vitro preparations of kidney containing interrenal tissue. Normally, 0.3-0.65 ng/5 min corticosterone and 0.15-0.3 ng/5 min aldosterone were released from the tissue. Regulatory peptides were effective in the following range: ACTH = arginine vasotocin > urotensin II > angiotensin II. They stimulate an elevation of corticosterone (plus 0.2-1 ng/5 min) and of aldosterone (plus 0.05-0.15 ng/5 min). The three primary effector systems leading to second messengers, adenylate cyclase (forming cAMP), phospholipase C (forming InsP3 + DAG), and phospholipase A2 (liberating arachidonic acid) are involved in stimulation of biosynthesis. It can be suggested that the second messengers stimulate the biosynthesis at the level of the steps between pregnenolone and corticosterone ('3 beta-hydroxysteroid-dehydrogenase etc.), because the release of corticosterone is more stimulated than aldosterone. This is different than the regulation of anuran interrenal tissue. Ca++ ions are involved in corticosterone secretion. Verapamil inhibits immediately the secretion of corticosteroids and elevation of external Ca++ stimulates the release. It is suggested that Ca++ mediates the secretion process itself. Metamorphosis does not change the response of the interrenal gland compared with the neotenic animal.
...
PMID:Regulation of interrenal secretion in the axolotl, Ambystoma mexicanum. 781 1

The secosteroid hormone 1,25(OH)2-vitamin D3 rapidly activates voltage-dependent Ca2+ channels of the L-type in skeletal and cardiac muscle cells by a non-genomic mechanism which involves guanine nucleotide binding (G) protein-medicated stimulation of the adenylate cyclase/cAMP/protein kinase A messenger system. Modifications in calmodulin intracellular distribution induced by PKA-dependent membrane protein phosphorylation may participate in the fast regulation of muscle Ca2+ influx by 1,25(OH)2D3. The protein kinase C pathway also plays a role modulating 1,25(OH)2D3 signal transduction in muscle by cross-talk with the PKA system. The hormone sequentially activates phospholipases C and D providing diacylglycerol for PKC activation and inositol triphosphate for intracellular Ca2+ mobilization. In addition, 1,25(OH)2D3 rapidly stimulates phospholipase A2 generating arachidonic acid for the eicosanoid pathway. Specificity of hormone effects suggests that binding to a muscle membrane-bound receptor mediates these events.
...
PMID:Non-genomic signal transduction pathway of vitamin D in muscle. 788 98

Cellular responses to changes in the extracellular environment are mediated by intracellular signaling systems. One of the most extensively studied systems is adenylate cyclase which generates the second messenger molecule cAMP. Another one is the phosphatidylinositol (PI) second messenger system giving rise to IP3 and diacylglycerol, the latter stimulating protein kinase C. Recently, a third potential signaling system has attracted increased scientific attention: the phospholipase A2 system which generates arachidonic acid. This substance may be used for eicosanoid synthesis or serve as a second messenger molecule. The present report gives more evidence about mechanisms how these signaling pathways interact in cultured astrocytes. Substances commonly used for stimulation of arachidonic acid release and prostaglandin synthesis in these cultures (A23187, TPA) had no influence on intracellular cAMP levels. Pertussis toxin that had previously been shown to inhibit prostaglandin synthesis, had no influence on cAMP levels either. Cholera toxin, however, raised intracellular cAMP significantly, although much less than the beta-adrenoceptor agonist isoproterenol. Cholera toxin also caused a marked change in astroglial morphology even at reduced concentrations (1-10 ng/ml). A23187 used in combination with Ctx had a moderate stimulatory effect on cAMP synthesis. In contrast, in the presence of Ctx, the PKC-activating phorbol ester TPA synergistically stimulated cAMP production, raising cAMP levels as high as isoproterenol-stimulated levels. The TPA effect was concentration-dependent. It was also dependent on an intact PKC since preincubation of cells with the phorbol ester completely abolished the synergistic effect. The synergistic effect of the phorbol ester was also observed at subthreshold concentrations of isoproterenol. The data reveal that the sole activation of most Gs molecules is a necessary but not sufficient prerequisite to achieve maximal adenylate cyclase activity. The fine-tuning of this activity apparently occurs at the catalytic subunit which is under the (partial) control of phosphorylation by PKC.
...
PMID:The phorbol ester TPA potentiates cholera toxin- and isoproterenol-stimulated cyclic AMP-synthesis in primary astrocyte cultures. 790 11

The role of intracellular signal transduction mechanisms in regulating the motility and metabolism of rat spermatozoa in undiluted caudal epididymal fluid (CEF) was examined. Samples of CEF containing immotile spermatozoa were exposed to drugs and other agents that either stimulate signal transduction pathways or mimic the action of their second messengers. Under these conditions, sperm motility in 25-30 nl of CEF was stimulated by calcium ions (Ca2+), N2,2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate (dibutyryl cGMP), cyclic adenosine 3':5'-monophosphate (cAMP), N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cAMP), 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cAMP), caffeine, theophylline and bicarbonate ions (HCO3-). Other agents such as magnesium ions (Mg2+), veratridine, phospholipase C (PLC), ionophore A23187, 1,2-dioctenoyl-sn-glycerol (DAG), phorbol 12-myristate 13-acetate, phospholipase A2 (PLA2), arachidonic acid, and melittin did not significantly influence motility. In the presence of radiolabelled energy substrates, untreated (immotile) spermatozoa in samples of CEF utilised D-[U-14C]glucose and [1-14C]acetate as exogenous energy sources for oxidative metabolism. No detectable 14C-lactate was produced, and none of the drugs altered the rate of glycolytic or oxidative metabolism. The findings suggest that the motility of rat caudal epididymal spermatozoa is regulated by Ca2+ and the guanylate cyclase and adenylate cyclase pathways, but not through the PLC and PLA2 pathways. Also, their metabolism of exogenous substrate was uncoupled from the induction of motility, and their oxidative capacity exceeded the rate of flux of glucose-carbon through the glycolytic pathway.
...
PMID:Intracellular signal transduction mechanisms of rat epididymal spermatozoa and their relationship to motility and metabolism. 804 68


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

---