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)

Recent evidence suggests that the histamine receptor blocking agent cimetidine can decrease parathyroid hormone release from human parathyroids. To determine the mechanism for inhibition we examined the ability of histamine 1 X 10(-5) moles/liter to stimulate adenylate cyclase in a particulate membrane preparation from 13 human parathyroid glands. Histamine significantly increased adenylate cyclase activity as compared to control; however, the degree of stimulation was variable among the individual tissue samples. Enzyme stimulation was dose dependent over the concentration range of 1 X 10(-7) to 1 X 10(-4) moles/liter. Cimetidine at 1 X 10(-4) moles/liter completely abolished the histamine mediated increase in activity, but did not block the epinephrine-induced stimulation. The identification of an adenylate cyclase system in certain human parathyroid adenomas that is stimulated by histamine and blocked by cimetidine may offer a basis for the pharmacologic alteration of parathyroid hormone secretion.
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PMID:Human parathyroid adenoma adenylate cyclase: stimulation by histamine that is blocked by cimetidine. 724 69

In a preliminary study, the stimulatory effect of histamine on an adenylate cyclase system in a solubilized cell-free preparation of the rat hypothalamus was established. The effect was dose dependent, and the histamine concentration required for half-maximal activation (Ka) was determined at 0.1 muM. At a 10-fold higher concentration, both chloropyramine, the classical histamine H1 antagonist, and metiamide, the selective H2-receptor blocker, partially blocked this action. Experiments carried out in hypothalamic slices showed a stimulatory effect of both the H1-agonist, 2-(2-pyridyl)-ethylamine, and the H2-antagonist, dimaprit, on adenylate cyclase in the range of histamine action. These effects could be reversed completely by the H1-antagonist, mepyramine, and the H2-receptor blocker cimetidine. In an additional study, histamine, histamine agonists and antagonists were tested on the spontaneous and the potassium-activated outflow of 3H-noradrenaline from rat hypothalamic slices. Histamine did not modify this outflow significantly, whereas the H1-agonist 2-(2-pyridyl)-ethylamine, produced a marked, dose-related increase in both the spontaneous and the potassium-stimulated release of noradrenaline. The H2-receptor blocker, cimetidine, also exerted a moderate but statistically significant stimulatory effect in this system. In combination studies, the noradrenaline-releasing action of these compounds could not he reversed by the selectively acting histaminic or antihistaminic agents, showing that this effect does not relate to the histaminic or antihistaminic property of the compound. It is becoming clear that histamine exerts a direct stimulatory effect on hypothalamic adenylate cyclase. The noradrenaline-releasing potency of some histaminic and antihistaminic agents showed that these compounds might modify the clear histamine effects through the release of other transmitter amines.
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PMID:Additional data on the function of hypothalamic histamine. 724 43

The possible presence of histamine H2 receptors in dog ventricle was investigated by determining the effect of histamine on adenylate cyclase prepared from that tissue. Epinephrine produced a dose-dependent increase in adenylate cyclase activity but histamine had no effect. Histamine H2 receptors probably do not exist in dog ventricle.
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PMID:The effect of histamine and epinephrine on adenylate cyclase prepared from dog ventricle. 745 3

Nimesulide (NIM) is a sulfonanilide nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of various inflammatory diseases and chemically unrelated to other acidic NSAIDs, such as acetylsalicylic acid (ASA) and indomethacin (INDO). We investigated the effects of NIM and of its in vivo metabolite, 4-hydroxy-NIM (OH-NIM), on the release of performed (histamine) and de novo synthesized mediators (sulfidopeptide leukotriene C4 [LTC4] and prostaglandin D2 [PGD2]) from human basophils and mast cells isolated from lung parenchyma (HLMC) and skin (HSMC). Histamine release from basophils challenged with rabbit anti-human IgE antibody (anti-IgE) was enhanced by preincubation with ASA or INDO (92.2 +/- 7.1% at 10(-3) M and 61.1 +/- 6.7% at 3 x 10(-6) M, respectively; P < .001). In contrast, NIM and its metabolite, OH-NIM (10(-6) to 10(-3) M), caused concentration-dependent inhibition (2.9 to approximately 60% and 3.7 to approximately 90%, respectively) of IgE-mediated histamine release from basophils. NIM and OH-NIM also inhibited histamine release from basophils induced by the Ca++ ionophore A23187 and different protein kinase C activators, such as 12-O-tetradecanoyl-phorbol-13-acetate, bryostatin 1 and bryostatin 5. NIM and OH-NIM also inhibited the IgE-mediated histamine release from HLMC (52.3 +/- 9.6% and 66.1 +/- 12.1% at 10(-3) M, respectively; P < .0001) and HSMC (67.3 +/- 3.7% and 77.7 +/- 12.0% at 10(-3) M, respectively; P < .0001) but had little or no effect on HLMC and HSMC activated by A23187. NIM (10(-6) to 10(-3) M) markedly inhibited the de novo synthesis of LTC4 from basophils, LTC4 and PGD2 from HLMC and PGD2 from HSMC. NIM and OH-NIM potentiated, whereas ASA and INDO reversed, the inhibitory effect of adenylate cyclase agonists, such as prostaglandin E1 and forskolin. In addition, NIM and OH-NIM reversed the enhancing effects of ASA and INDO on IgE-mediated histamine release from basophils.
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PMID:Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells. 750 32

The regulation of interleukin (IL)-6 synthesis by cAMP-increasing agents remains an unresolved issue. Since an increase in cAMP levels via activation of histamine H2 receptors does not induce IL-1 beta synthesis but enhances self-induction of IL-1 (Vannier, E., and Dinarello, C. A. (1993) J. Clin. Invest. 92, 281-287), we investigated whether histamine regulates IL-6 synthesis. Human peripheral blood mononuclear cells were stimulated with IL-1 alpha in the absence or presence of histamine (1 nM to 100 microM). IL-6 was measured using a specific radioimmunoassay. Histamine alone did not induce protein synthesis or mRNA accumulation for IL-6. Histamine (1-100 microM) enhanced IL-1 alpha-induced synthesis of IL-6 (p < 0.001). Cimetidine and ranitidine, H2 receptor antagonists structurally unrelated to each other, completely reversed the histamine-mediated increase in IL-1 alpha-induced IL-6 synthesis. However, diphenhydramine, an H1 receptor antagonist, did not reverse this effect. Prostaglandin E2, an activator of adenylate cyclase, also enhanced IL-1 alpha-induced synthesis of IL-6. Histamine increased and sustained steady-state levels of IL-6 mRNA in IL-1 alpha-stimulated cells, but reduced IL-6 mRNA half-life (3.5 h versus 1.8 h). Our results indicate that cAMP-increasing agents, such as histamine or prostaglandin E2, fail to induce IL-6 synthesis but rather enhance IL-1-induced IL-6 synthesis.
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PMID:Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. 751 96

This study investigates the interaction between histamine and the adenylate cyclase systems involved in the secretion of amylase from the guinea-pig pancreatic lobules. Histamine increased amylase release, reaching a maximum response at 10(-5) M. Similarly, vasoactive intestinal peptide (VIP) evoked significant increase in amylase release, though not in a dose-dependent fashion. When the pancreatic lobules were incubated with histamine in combination with VIP, forskolin or 3-isobutyl-1-methylxanthine (IBMX), amylase secretion was increased as compared to histamine alone. The stimulatory effect of VIP was also increased by the presence of forskolin or IBMX. These findings suggest that in guinea-pig pancreatic lobules, VIP, forskolin and IBMX, agents involved in the cyclic adenosine monophosphate (cAMP) pathway, potentiate histamine stimulated amylase release.
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PMID:Histamine and the cAMP pathway in the guinea-pig pancreas. 753 75

Histamine, a ubiquitous cell-to-cell messenger, exerts its numerous actions through interaction with three pharmacologically distinct receptor subtypes, termed H1, H2 and H3. The design of selective agonists and antagonists has allowed to establish their respective pharmacological profile. Radioligand binding studies and, very recently, molecular biological studies have shown that they all belong to the superfamily of G-protein coupled receptors. H1 and H2-receptor antagonists have been successfully used for a long time in the treatment of allergy and ulcer, respectively. Some of them have been designed as highly potent and selective radioligands and have allowed to analyze the precise distribution of H1 and H2 receptors in various tissues including the brain. Recently, H1- and H2-receptor genes have been cloned in various animal species. Transfection of mammalian cells with these intronless genes has confirmed the respective coupling of H1 and H2 receptors with phospholipase C and adenylylcyclase. However, other known or unknown intracellular signals, could also be triggered by the stimulation in a transfected cell of a single H1 or H2 receptor through coupling to different G-proteins. A third histamine receptor subtype, the H3 receptor was evidenced in rodent and human brain by the inhibition of histamine release and synthesis it mediates in various areas. Thus, H3 receptors were considered as autoreceptors localized on histaminergic terminals. With the design of several potent and selective H3-receptor agonists and of an antagonist thioperamide, the critical role of H3 receptors in the control of histaminergic neurons in vivo was established.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological properties of histamine receptor subtypes. 792 Jan 74

In porcine gastric mucous cells, isolated enzymatically from the fundic mucosa and enriched by counterflow centrifugation, PGE2 (1 microM) increased adenylate cyclase activity to 225% and, distinct from that documented for other species, also [Ca2+]i, measured fluorimetrically with Fura2/AM, in Ca(2+)-containing and Ca(2+)-free incubation medium to 182% and 165% of control values, respectively. PGF2 alpha, PGD2, the stable prostacyclin analogue iloprost and the thromboxane-mimetic U46619 had no significant effects on adenylate cyclase activity and [Ca2+]i. Histamine (10 microM) stimulated adenylate cyclase activity to 236% of control value, an effect which could be blocked by the H2-receptor antagonist ranitidine. However, histamine and the activators of the cAMP system forskolin and dibutyryl cAMP had no significant effect on [Ca2+]i, indicating that an activation of the adenylate cyclase/cAMP system per se does not result in an increase in [Ca2+]i. These data suggest that prostanoids stimulate adenylate cyclase activity and [Ca2+]i in gastric mucous cells via activation of EP-receptors linked to both second messenger systems.
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PMID:Effects of prostaglandins on [Ca2+]i and adenylate cyclase activity in isolated porcine gastric mucous cells. 794 38

The H(+)-K(+)-adenosinetriphosphatase (ATPase) is expressed in the parietal cell and is responsible for acid secretion by the stomach. Histamine binds to an H2 receptor and activates adenylate cyclase and intracellular calcium concentration ([Ca2+]i) elevation, stimulating acid secretion. It has been shown that omeprazole administered to rats increases serum gastrin and transiently increases the level of mRNA for the alpha-subunit of the pump, but this increase is blocked by the presence of the H2-receptor antagonist, famotidine [A. Tari, G. Yamamoto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs, and J. H. Walsh. Am. J. Physiol. 265 (Gastrointest. Liver Physiol. 28): G752-G758, 1993]. These observations suggest that the release of histamine induced by gastrin is essential for the increase of the expression of mRNA induced by omeprazole. Infusion of histamine at 15 mumol.kg-1.h-1 i.v. for 1 h increased the alpha-subunit mRNA level by 144 +/- 2.4% and induced a stimulated morphological appearance of the parietal cell. These changes were inhibited completely by the competitive H2-receptor antagonist famotidine, which elevated gastric pH and serum gastrin. Famotidine also reduced the level of H(+)-K(+)-ATPase mRNA compared with control animals. No change in the expression of beta-actin mRNA was observed in any group of animals. These data provide direct evidence for histamine stimulation of H(+)-K(+)-ATPase alpha-subunit gene expression by activation of the H2 receptor.
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PMID:Effect of histamine on rat gastric H(+)-K(+)-ATPase alpha-subunit expression. 816 83

The influence of histamine on the basal intracellular free Ca2+ concentration ([Ca2+]i) and agonist-induced increases of [Ca2+]i was studied in Fura-2-loaded neutrophils. Histamine was unable to change the basal [Ca2+]i at concentrations (10(-6)-10(-4) M) that have been shown to cause a rapid increase in [Ca2+]i in a variety of cell types. Histamine, in contrast, was found to inhibit dose-dependently the rise in [Ca2+]i induced by two neutrophil receptor agonists, N-formylmethionyl-leucylphenylalanine (fMLP) and serum-opsonized zymosan particles. The histamine inhibition was shown to be specific for H2 receptor activation by blocking experiments with selective H1 and H2 receptor antagonists. In the absence of extracellular Ca2+, histamine failed to inhibit the agonist-induced rise in [Ca2+]i, indicating that histamine does not affect the release of Ca2+ from internal pools. Forskolin, which mimics the biochemical effects of H2 receptor activation by directly stimulating adenylate cyclase, also decreased the Ca2+ transients induced by receptor agonists. Similarly, 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, reduced the Ca2+ response of activated neutrophils. These data suggest that in human neutrophils (1) no functional H1 receptors are present or alternatively H1 receptors are not coupled to cellular Ca2+ metabolism, and (2) H2 receptors modulate the receptor-triggered Ca2+ flux via the cAMP second messenger system.
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PMID:Histamine modulation of Ca2+ homeostasis in human neutrophils. 824 11


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