H<sub>3</sub> receptor antagonist, thioperamide, inhibits adrenal steroidogenesis and histamine binding to adrenocortical microsomes and binds to cytochrome P450

LaBella, Frank S.; Queen, Gary; Glavin, Gary B.; Durant, G. J.; Stein, Douglas; Brandes, Lorne J.

doi:10.1111/j.1476-5381.1992.tb14480.x

Cited by 50 publications

(27 citation statements)

References 22 publications

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“…Although H 3 R agonists contain the imidazole ring, which inhibits P450 isozymes through coordination with their heme moiety, they lack the lipophilic side chain present in antagonists. Consistent with their resulting weak potency at liver microsomes (Brandes et al, 1998) and adrenal P450 enzymes (LaBella et al, 1992;Yang et al, 2002), HA and H 3 R agonists failed to affect the non-H 3 R binding at concentrations up to 0.1 mM. As already reported (Ligneau et al, 1994), the agonist imetit was allowed to discriminate the specific (H 3 R) from the nonspecific (non-H 3 R) binding, although the latter was much higher.…”

Section: Discussionsupporting

confidence: 54%

“…First, the non-H 3 R binding was fully displaced by ketoconazole, an imidazole-containing broad-spectrum cytochrome P450 inhibitor, with a consistent submicromolar potency (Higashi et al, 1987;Yang et al, 2002). Second, it was also fully inhibited by the three imidazole-containing compounds, ciproxifan, thioperamide, and clobenpropit, with submicromolar potencies similar to those found at adrenal P450 enzymes (LaBella et al, 1992;Yang et al, 2002) but two orders of magnitude lower than their affinities at rat H 3 Rs (Stark et al, 2001). Although H 3 R agonists contain the imidazole ring, which inhibits P450 isozymes through coordination with their heme moiety, they lack the lipophilic side chain present in antagonists.…”

Section: Discussionmentioning

confidence: 75%

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Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

Davenas¹,

Rouleau²,

Morisset-Lopez³

et al. 2008

J Pharmacol Exp Ther

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Previous studies have suggested that histamine (HA) acts as an autocrine growth factor. We have explored the modulation of cell proliferation by HA using McA-RH7777 hepatoma cells. High L-histidine decarboxylase (HDC) expression and HA synthesis were found in McA-RH7777 cells. Whereas extracellular HA reached submicromolar concentrations, intracellular levels were very low, indicating that HA was secreted by the cells.McA-RH7777 cells also express H 3 -receptor (H 3 R) transcripts and proteins. Reverse transcriptase-polymerase chain reaction analysis detected only transcripts for the long isoform. Immunocytochemistry performed with a selective H 3 R antibody showed that most cells were immunoreactive. H 3 R binding sites (B max ϳ30 fmol/mg protein) were identified when [125 I] iodoproxyfan binding was displaced by the agonist imetit. High-affinity binding also occurred at cytochrome P450 enzymes. This binding was not inhibited by HA, H 3 R agonists, or by a nonimidazole H 3 R antagonist but was displaced by imidazole H 3 R antagonists or by ketoconazole, a imidazolecontaining cytochrome inhibitor. HA inhibited proliferation of McA-RH7777 hepatoma cells. The absence of uptake system, its much higher potency at H 3 Rs, and its low intracellular levels suggested that HA interacted with H 3 Rs rather than cytochromes. In agreement, both imidazole H 3 R antagonists, a nonimidazole H 3 R antagonist, and the HDC inhibitor ␣-monofluoromethyl histidine increased cell proliferation (up to ϳ60%), revealing a H 3 R-mediated inhibition by endogenous HA. Moreover, exogenous HA inhibited the increase induced by ␣-FMH or H 3 R antagonists with a nanomolar potency. In conclusion, our findings show that HA regulates proliferation of McA-RH7777 hepatoma cells by interacting with autoinhibitory H 3 Rs.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 75%

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

Davenas¹,

Rouleau²,

Morisset-Lopez³

et al. 2008

J Pharmacol Exp Ther

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“…Whatever the real value of K0.5, it is more than one order of magnitude lower than previously reported for other heme proteins. Indeed cytochrome P450 has an affinity for histamine of 16 #M (12). Similarly, the affinity reported for thromboxane synthase for imidazole and histamine were of 46 #M and >500 #M, respectively (based on inhibition of thromboxane B2 synthesis) (8).…”

mentioning

confidence: 97%

High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.

Ribeiro

Walker

1994

The Journal of Experimental Medicine

140

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Summal'yThe salivary glands of Rhodnius prolixus contain a nitrosyl-heme protein, named nitrophorin, that releases the vasodilatory and antiplatelet compound nitric oxide (NO). Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins. Both imidazole and histamine, but not histidine can produce full change of the difference spectra of the Soret band in the 1-3 #M concentration range (at a heme protein concentration of 0.4 #M). The apparent Ko.5 for the binding of histamine with the heme protein is below 1 #M. Furthermore, the complex histamine-heme protein does not dissociate after molecular sieving chromatography. To investigate whether histamine could displace NO from the native nitrosyl nitrophorins, histamine was added to the native heme proteins, leading to displacement of the bound NO as observed by changes in the absorption spectra as well as by the production of nitrite. Finally, the antihistamine effect of the heme protein was demonstrated by its inhibition of the histamine-provoked contractures of the guinea pig ileum. It is concluded that histamine, a common autacoid found at the site of injury and exposure to antigenic substances such as the site of feeding by hematophagous arthropods, can be scavenged by the nitrosyl nitrophorin of R. prolixus, which, in return, will release the vasodilatory and platelet inhibiting NO to counteract the host hemostatic response.

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“…Potential interaction of imidazole H 3 R antagonists with cytochrome P450 enzymes is also of note since metyrapone, a cytochrome P450 inhibitor, markedly improves the specific H 3 R binding of radiolabeled thioperamide and clobenpropit (Alves-Rodrigues et al, 1996;Harper et al, 1999). In addition, thioperamide has been shown to bind cytochrome P450 enzymes and inhibit adrenal steroidogenesis (Labella et al, 1992). Interestingly, the imidazole moiety is found in other drug molecules that have been shown to inhibit this important metabolic pathway (Halpert et al, 1994).…”

mentioning

confidence: 99%

Two Novel and Selective Nonimidazole Histamine H₃ Receptor Antagonists A-304121 and A-317920: I. In Vitro Pharmacological Effects

Esbenshade

Krueger²,

Miller³

et al. 2003

J Pharmacol Exp Ther

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Histamine H 3 receptor (H 3 R) antagonists enhance neurotransmitter release and are being developed for the treatment of a variety of neurological and cognitive disorders. Many potent histamine H 3 R antagonists contain an imidazole moiety that limits receptor selectivity and the tolerability of this class of compounds. Here we present the in vitro pharmacological data for two novel piperazine amide ligands,

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H₃ receptor antagonist, thioperamide, inhibits adrenal steroidogenesis and histamine binding to adrenocortical microsomes and binds to cytochrome P450

Cited by 50 publications

References 22 publications

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.

Two Novel and Selective Nonimidazole Histamine H₃ Receptor Antagonists A-304121 and A-317920: I. In Vitro Pharmacological Effects

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H3 receptor antagonist, thioperamide, inhibits adrenal steroidogenesis and histamine binding to adrenocortical microsomes and binds to cytochrome P450

Cited by 50 publications

References 22 publications

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H3Receptors

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H3Receptors

High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.

Two Novel and Selective Nonimidazole Histamine H3 Receptor Antagonists A-304121 and A-317920: I. In Vitro Pharmacological Effects

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Product

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H₃ receptor antagonist, thioperamide, inhibits adrenal steroidogenesis and histamine binding to adrenocortical microsomes and binds to cytochrome P450

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

Autoregulation of McA-RH7777 Hepatoma Cell Proliferation by Histamine H₃Receptors

Two Novel and Selective Nonimidazole Histamine H₃ Receptor Antagonists A-304121 and A-317920: I. In Vitro Pharmacological Effects