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

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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)

The distribution and classification of histamine receptors in mammalian and avian tissues have been summarized in Tables 1-4. It is evident that histamine receptors are present on a number of morphologically distinct cell types and the proportion of cells bearing H1- and H2-receptors varies not only with the species but also with the cell source. The pharmacological receptors mediating mepyramine-sensitive histamine responses have been defined as H1-receptors. Receptors mediating mepyramine-resistant, but burimamide or metiamide-sensitive histamine responses have been classified as H2-receptors. Histamine responses mediated via H2-receptors seem to involve the adenylcyclase system resulting in elevation of intracellular cyclic-AMP level, which is susceptible to burimamide blockade but insensitive to beta-adrenergic blocking agents. This mode of action of histamine involving H2-receptors and the adenyl cyclase system has been shown to stimulate the mammalian heart; promote gastric acid secretion; inhibit antigen-induced histamine release from leucocytes and inhibit lymphocyte-mediated cytotoxicity. It can further be concluded that both H1- and H2-receptors are widely distributed throughout the animal body in the gastro-intestinal, reproductive, respiratory and cardiovascular systems, nervous system and on mast cells and blood leucocytes. In these tissues, histamine receptors play an important role in physiological, immunological and immunopathological processes. Interaction of histamine with both H1- and H2-receptors in varying proportions modulates the overall manifestation of cardiovascular and respiratory syndromes during certain immunopathological conditions (e.g. inflammation, allergy and anaphylaxis). Histamine receptors also appear to play and important role in the development of immuno-competence and immunity.
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PMID:Classification and biological distribution of histamine receptor sub-types. 0 79

We have investigated the effect of NZ-107, an inhibitor of bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS-A), on tracheal responses to adenosine in the guinea pig. In the presence of an adenosine uptake inhibitor, dipyridamole (1 microM), NZ-107 (0.3-1 microM) enhanced adenosine-induced relaxation in 30 nM leukotriene D4 (LTD4)-precontracted trachea, whereas aminophylline (AP, 10-30 microM), an adenosine receptor antagonist, markedly inhibited it. NZ-107 (1 microM) also enhanced the relaxation induced by forskolin, an adenylate cyclase activator, but not that by nitroprusside (NP), a guanylate cyclase activator. AP (30 microM) affected neither forskolin- nor NP-induced relaxation. NZ-107 (1 microM) and AP (30 microM) inhibited to about the same extent the contractile response to an adenosine A1 receptor agonist, the R(-)-enantiomer of N6-(2-phenylisopropyl)-adenosine (R-PIA). The R-PIA-induced contraction was completely blocked by 5 microM indomethacin. NZ-107 (1 microM) did not affect the contraction induced by PGD2, but significantly reduced that of PGF2 alpha. AP (30 microM) had no effect on PGF2 alpha- and PGD2-induced contractions. These results suggest that NZ-107 may have a unique profile for adenosine responses in bronchial asthma.
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PMID:Effects of NZ-107 on tracheal responses to adenosine in the guinea pig. 188 Sep 89

The existence of cardiac h1- and h2-receptors is evidenced by pharmacologic studies. Despite of the relatively high content of cardiac histamine it is not clarified whether histamine actually plays a physiologic role - apart from pharmacologic effects - in the regulation of myocardial function and coronary blood flow. Under pathophysiologic conditions (during anaphylaxis, surgical procedures, accidents, stress etc.), however, when a local or systemic histamine release occurs both hemodynamic and arrhythmogenic effects are evident. Numerous studies in animal models conclusively demonstrated a role of cardiac histamine as a major mediator of serious arrhythmias. Consequently, a combination of h1- and h2-receptor antagonists (f.e. Dimetinden/Cimetidin) was recommended as a prophylactic treatment against severe anaphylaxis including life-threatening arrhythmias for cardiac patients at risk. There is pharmacologic evidence of both a positive inotropic and chronotropic effect in the human heart via h2-receptor and stimulation of adenylate cyclase. Histamine-induced coronary effects such as vasoconstriction via h1-receptor and coronary dilatation via h2-receptor are not yet sufficiently validated. Studies on the human heart in vitro using coronary strips from explanted hearts and in vivo investigations on the intact coronary system yielded conflicting results. H2-receptor blocking agents cimetidine, ranitidine and famotidine have qualitatively a different pharmocodynamic spectrum of side effects due to differences in chemical structure. Data on cardiac arrhythmias are mostly associated to cimetidine. Symptomatic bradycardia were reported for both ranitidine and cimetidine. A possible negative inotropic effect of famotidine, although presently not validated, requires further studies. Causative and adverse side effects of cimetidine on the cardiovascular system, however, are to be expected extremely seldom due to easily reversible competetive h2-receptor binding. For prophylaxis rapid intravenous injections of h2-blockers, particularly in elder patients with cardiac diseases, should be avoided. Compared to cimetidine, a tendency of explainable difference seems to become apparent for ranitidine and famotidine due to higher receptor affinity.
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PMID:[Histamine effects on the heart with special reference to cardiac side effects of H2 receptor antagonists]. 257 Jan 78

Though the precise etiology of anaphylactoid contrast media reactions is unknown, recent investigations have contributed important insight into their pathogenesis. Explorations of the complement and coagulation systems, the basophil histamine release system, and antigen-IgE interactions are summarized. Current investigations focusing on the contact system are discussed. Patients with asthma and patients who are contrast material reactors show increased prekallikrein transformation rates indicating increased contact system activity. Increased endogenous heparin-like material was found in asthmatic patients and in 50% of prechallenge citrated plasmas of patients who later developed contrast reactions, suggesting partial explanation of increased incidence of reactions in asthmatics. Elevated heparin-like material may have pathogenic significance; it may potentiate prekallikrein transformation and inhibit adenylate cyclase to induce release of inflammatory mediators and produce bronchospasm. When appropriately administered, glucocorticoids appear to protect against contrast reactions. Incidence of systemic anaphylaxis with nonionic contrast media is unknown but is expected to be less than that with ionic media. Additional experience is needed to assess this potential benefit of nonionics.
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PMID:Etiology of anaphylactoid responses. The promise of nonionics. 257 45

Components of the cyclic nucleotide system--cAMP, cGMP, activities of adenylate cyclase (AC) and phosphodiesterase (PDase) were studied in brain, lung, adrenal gland, liver tissues, in blood plasma (cAMP, cGMP) and in leukocytes (AC and PDase) of guinea pigs at the periods of sensibilization and development of anaphylaxis. Dibutyryl cAMP was preadministered in a number of the animals in order to correct possible alterations in the system of cyclic nucleotides and to stimulate unspecific resistance of the organism. Distinct alterations were observed in the patterns studied after sensibilization of the animals, especially pronounced in anaphylactic shock. Preadministration of dibutyryl cAMP prevented development of anaphylactic shock in all the animals treated with the antigen. Even after repeated administration of the antigen the antigen. Even after repeated administration of the antigen the anaphylactic shock was observed only in 50% of these animals. The data obtained suggest that synthetic analogues of cAMP may be used for treatment of patients with allergic disorders.
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PMID:[Changes in the cyclic nucleotide system in experimental anaphylaxis and approaches to their correction]. 299 23

Anaphylaxis to known allergens occurred in two patients under treatment for hypertension with propranolol. The clinical course of both cases was similar. Bradycardia associated with an undetectable blood pressure, unusual severity, and sluggish response to treatment were major common factors in which blockade of the beta-adrenergic system may have had a role. Propranolol, a beta-adrenergic antagonist that acts competitively by blocking the adenylate cyclase receptor on efferent cells, is well recognized to cause increased airways resistance in some asthmatic and normal subjects. It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release. The bradycardia during profound hypotension is attributed to an unopposed cholinergic action caused by blunting of the normal endogenous beta-adrenergic response by propranolol.
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PMID:Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. 611 16

Studies have demonstrated greater hazards associated with anaphylaxis in patients receiving beta-blockers. Serious anaphylaxis is more frequent. Evidence suggests this occurs via modulation of adenylate cyclase, which can influence release of anaphylactogenic mediators. Treatment of anaphylaxis in patients exposed to beta-blockers is complicated because therapeutic administration of epinephrine (adrenaline) may be ineffective or promote undesired alpha-adrenergic and vagotonic effects. Risk reduction efforts should be considered for patients receiving beta-blockers who are prone to experience anaphylaxis.
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PMID:Anaphylactoid and anaphylactic reactions. Hazards of beta-blockers. 766 59

The inflammatory exudate at the post-anaphylaxis phase of allergic inflammation in rats has an ability to enhance histamine production by bone marrow cells. To analyze the mechanism of the inflammatory exudate-induced histamine production pharmacologically, the effects of several drugs were examined in cultures of bone marrow cells. Incubation of the bone marrow cells in the presence of the inflammatory exudate that had been centrifuged and dialyzed against Hanks' balanced salt solution increased histidine decarboxylase activity in the cells and histamine concentration in the conditioned medium. The induction of histamine production by the inflammatory exudate was inhibited by actinomycin D (0.01-1 microM), an inhibitor of RNA synthesis, and cycloheximide (0.1-10 microM), a protein synthesis inhibitor. The protein kinase C inhibitors staurosporine (2-20 nM), K-252a (6-200 nM), and H-7 (10.3-103 microM) also inhibited the inflammatory exudate-induced histamine production in a concentration-dependent manner. The tyrosine kinase inhibitor genistein (3.7-37 microM) also inhibited the inflammatory exudate-induced histamine production, but the protein kinase A inhibitor H-89 (0.2 microM), and the adenylate cyclase activator forskolin (0.1 microM) showed no effect. These findings suggest that histamine production induced by the inflammatory exudate is mediated by the de novo synthesis of histidine decarboxylase and by the activation of protein kinase C and tyrosine kinase.
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PMID:Pharmacological analysis of the inflammatory exudate-induced histamine production in bone marrow cells. 913

RO 25-1553 is a synthetic VIP analogue that induced a long-lasting relaxation of tracheal and bronchial smooth muscles as well as a reduction of edema and eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP receptor subclasses and to stimulate adenylate cyclase activity. The cellular models tested expressed one single receptor subtype: Chinese hamster ovary (CHO) cells transfected with the rat recombinant PACAP I, rat VIP1, and human VIP2 receptors; SUP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells expressing the human VIP1 receptor. RO 25-1553 was threefold more potent than VIP on the human VIP2 receptor, 100- and 600-fold less potent than VIP on the rat and human VIP1 receptors, respectively, and 10-fold less potent than VIP and 3000-fold less potent than PACAP on the PACAP I receptor. RO 25-1553 was a full agonist on the VIP2, the PACAP I, and the rat recombinant VIP1 receptor but a partial agonist only on the human VIP1 receptor. Thus, RO 25-1553 is a highly selective agonist ligand for the VIP2 receptor subclass.
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PMID:The long-acting vasoactive intestinal polypeptide agonist RO 25-1553 is highly selective of the VIP2 receptor subclass. 914 28

Leukotriene D4 (LTD4) is one of the slow-reacting substances of anaphylaxis and is reported to have a diverse response including the mediation of glomerular nephritis. However, little is known about the functions of LTD4 and its mechanisms of action in primary cultured rabbit renal proximal tubular cells (PTCs). The purpose of this study is to investigate the effect of LTD4 on Na+ uptake and its related signal transduction pathways in PTCs. LTD4 (>10(-9) M) significantly inhibited the Na+ uptake after 15 min (in nmol/mg protein: controls 431.7+/-11.4 vs. LTD4 (10(-9) M) 355.0+/-23.6; p<0. 05); and its effect was blocked by MK-571 (10(-6) M), a leukotriene receptor antagonist, in PTCs. Preincubation with cilastatin, a renal dipeptidase inhibitor, and polyclonal antibody against renal dipeptidase potentiated the inhibitory effect of LTD4 on Na+ uptake. SQ 22536 (10(-6) M), an adenylate cyclase inhibitor, and the myristoylated protein kinase A inhibitor amide 14-22 (PKI; 10(-5) M) blocked the effect of LTD4 on Na+ uptake (in nmol/mg protein: LTD4 349.9+/-18.5 vs. SQ 22536+LTD4 476.5+/-22.0 and PKI+LTD4 440.3+/-19. 3; p<0.05), and LTD4 induced an increase in cyclic adenosine monophosphate (cAMP), suggesting the involvement of cAMP in the inhibition of Na+ uptake. In addition, U 73122 (10(-6) M) and neomycin (10(-4) M), phospholipase C (PLC) inhibitors, W-7 (10(-4) M), a calmodulin antagonist, and bisindolylmaleimide I, a protein kinase C (PKC) inhibitor, blocked the LTD4-induced inhibition of Na+ uptake, strongly suggesting involvement of the PLC-PKC signal pathways in the effect of LTD4. LTD4 significantly increased [Ca2]i by 49+/-7% as compared with baseline. TMB-8 (10(-5) M) and BAPTA/AM (10(-5) M), intracellular calcium mobilization blockers, completely blocked the LTD4-induced inhibition of Na+ uptake (in nmol/mg protein: LTD4 347.6+/-19.0 vs. TMB-8+LTD4 436.4+/-22.3 and BAPTA/AM+LTD4 419.9+/-14.3; p<0.05); however, EGTA (1 mM), a calcium chelator, partially blocked the LTD4-induced inhibition of Na+ uptake. In conclusion, LTD4-induced inhibition of Na+ uptake may be involved in both cAMP and PLC-PKC signal pathways in PTCs. In addition, Ca2+, which comes from the intracellular Ca2+ mobilization, is primarily responsible for the LTD4-induced inhibition of Na+ uptake.
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PMID:Leukotriene D4 inhibits Na+ uptake through cAMP and PLC pathways in primary cultured renal proximal tubular cells. 1039 8


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