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)

We reported previously that atrial natriuretic factor (ANF) and the ANF clearance receptor binding peptide, C-ANF(4-23)-NH2 (C-ANF), inhibit catecholamine (CA) release from rat, nerve growth factor-treated pheochromocytoma cells (PC12 cells) by a guanylate cyclase independent mechanism. This mechanism is most likely a pertussis toxin (PTX)-sensitive inhibition of adenylate cyclase. This study examines the role of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), in mediating atrial natriuretic factor effects on depolarization-induced CA release from PC12 cells. The following evidence supports the hypothesis that the neuromodulatory action of atrial peptides is independent of increases in cGMP: 1) ANF does not potentiate the inhibitory effect of C-ANF on CA release or cAMP generation but still elevates cGMP concentrations in the presence of C-ANF; 2) the neuromodulatory effects of ANF and C-ANF are blocked or reversed by a membrane permeable analog of cAMP, dibutyryl cAMP; 3) ANF and C-ANF attenuate CA release in the presence of a maximally effective concentration of dibutyryl cGMP; 4) the inhibitory effect of dibutyryl cGMP is PTX-insensitive whereas the atrial peptide effect is blocked by PTX-pretreatment; and 5) dibutyryl cGMP is without effect on adenylate cyclase. These data are consistent with the hypothesis that ANF and C-ANF act via the ANF clearance (R2) receptor to suppress adenylate cyclase activity and neurotransmission.
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PMID:Neuromodulatory effects of atrial natriuretic peptides correlate with an inhibition of adenylate cyclase but not an activation of guanylate cyclase. 134 40

We have recently designed the first 125I-labelled probes specific for the histamine H1 and H2 receptors. These reversible and irreversible antagonists are among the most potent H1 and H2 ligands and have enabled investigations into the biochemical and pharmacological properties of these two receptors. In various brain animal species, the ligand binding peptide of the H1 and H2 receptors, as determined by photoaffinity labeling, resides within 56-59 kDa peptides. In contrast, in guinea pig heart, the ligand binding domain of the H1 receptor is characterized by a higher molecular weight (68 kDa), suggesting the presence of an isoform of this protein, clearly differentiable by this biochemical property but not by its pharmacology. The reversible 125I-probes allowed us to extend the pharmacology of these receptors in several biological preparations and in human brain, and to establish their interaction with G-proteins. A detailed mapping of H1 and, for the first time, of H2 receptors, has been achieved in guinea pig brain, establishing their presence in almost all brain areas. These experiments show that there is no correlation between the density of H2 receptor and the activity of adenylate cyclase sensitive to histamine suggesting a molecular heterogeneity of this receptor.
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PMID:Reversible and irreversible labelling of H1- and H2 -receptors using novel [125I] probes. 167 31

The binding of clathrin-coated vesicles, clathrin triskelions, and free clathrin light chains to calmodulin-Sepharose was compared. When isolated from bovine brain, all three components bound to calmodulin-Sepharose in the presence of calcium and could be eluted by its removal. In contrast, coated vesicles and triskelions isolated from bovine adrenal gland did not bind to calmodulin-Sepharose, although the free light chains from adrenal gland bound as effectively as those from brain. As distinct isoforms of the clathrin light chains are expressed by brain and adrenal gland, these results implicate the clathrin light chains as the calmodulin-binding component of coated vesicles and triskelions. Furthermore, the insertion sequences found in the neuron-specific isoforms, although not necessary for the binding of free clathrin light chains to calmodulin, must facilitate the interaction of heavy chain-associated light chains with calmodulin. Recombinant mutants of LCa, with deletions spanning the entire sequence, were tested for binding to calmodulin-Sepharose. Those mutants retaining structural integrity, as assessed by the binding of a panel of monoclonal antibodies, exhibited varying amounts of calmodulin binding activity. However, deletion of the carboxyl-terminal 20 residues abolished calmodulin interaction. Thus, the carboxyl terminus of LCa appears to constitute a calmodulin-binding site. Peptides corresponding to the carboxyl terminus of LCa or LCb inhibited the interaction of the light chains with calmodulin, suggesting that this region forms the calmodulin-binding site of both LCa and LCb. The carboxyl-terminal peptides of LCa and LCb inhibited the interaction of light chains with calmodulin approximately 10-fold less effectively than a calmodulin-binding peptide derived from smooth muscle myosin light chain kinase, but much more effectively than a calmodulin-binding peptide derived from adenylate cyclase. This comparison places the clathrin light chain-calmodulin interaction within the physiological range seen for other calmodulin-binding proteins.
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PMID:The interaction of calmodulin with clathrin-coated vesicles, triskelions, and light chains. Localization of a binding site. 783 75

A perforated patch recording method was used to determine how plating cells on laminin (20 microg ml(-1); >2 h) alters cholinergic regulation of L-type Ca(2+) current (I(Ca,L)) in atrial myocytes. Acetylcholine (ACh; 1 microm)-induced inhibition of basal I(Ca,L) was not different between cells on glass and laminin. However, stimulation of I(Ca,L) elicited by ACh withdrawal was significantly smaller in cells on laminin (10 +/- 2 %) than on glass (48 +/- 5 %) (P < 0.001). Stimulation of I(Ca,L) induced by either spermine-NO (200 microm), milrinone (10 microm), IBMX (100 microm) or forskolin (1 microm) was significantly smaller in cells plated on laminin than on glass. However, stimulation of I(Ca,L) by 100 microm 8-CPT-cAMP or intracellular dialysis with 50 microM cAMP was not different between cells plated on laminin or glass. Basal, forskolin- and IBMX-stimulated cAMP content was significantly smaller in cells plated on laminin than on glass. Stimulation of I(Ca,L) by ACh withdrawal was significantly smaller in cells plated on an alpha beta 1-integrin antibody (10 +/- 4 %) than on glass (3 +/- 6 %; P < 0.001). In cells on laminin, prior exposure to 100 microg ml-1 YIGSR, a laminin receptor-binding peptide, restored ACh-induced stimulation of I(Ca,L) (58 +/- 14 %)laminin alone (7 +/- 2 %; P < 0. 05). Addition of 20 microm cytochalasin D or 1 microM latrunculin A, agents that prevent actin polymerization, to cells on laminin restored ACh-induced stimulation of I(Ca,L). We conclude that laminin binding to beta 1 integrins acts in association with the actin-based cytoskeleton to attenuate adenylate cyclase activity. As a result, laminin inhibits NO-mediated stimulation of I(Ca,L) elicited by ACh withdrawal. Laminin-integrin signalling may be relevant to changes in autonomic regulation that occur during cardiac development and/or disease.
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PMID:Laminin acts via beta 1 integrin signalling to alter cholinergic regulation of L-type Ca(2+) current in cat atrial myocytes. 1087 99