Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles

Karaki, H; Kishimoto, Tadashi; Ozaki, H

doi:10.1016/0378-8741(87)90055-9

Cited by 4 publications

(8 citation statements)

References 16 publications

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“…Similar to previous studies on vascular and intestinal smooth muscles (Hider et al 1981a & b;Karaki et al 1986;Shi et al 2000Shi et al & 2001, the present study demonstrate that harmine, harman, and harmaline have spasmolytic effect on carbachol-, histamine-, and KCl-induced contractions in guinea-pig tracheal smooth muscles. Since the EC 50 values for each compound to relax these 3 different spasmogens are significantly different, the mechanisms of spasmolytic action of these 3 compounds appear to be multiple.…”

Section: Discussionsupporting

confidence: 92%

“…The present receptor binding study also suggests that inhibition of harmaline on smooth muscle Ca 2π channels is probably not due to an action on the 1,4-dihydropyridine binding site of L-type Ca 2π channels. Consistent with this result, Karaki et al (1986) showed that the inhibitory effect of harmaline on rabbit aorta and guinea-pig taenia was not reversed by Bay K 8644, a dihydropyridine which stimulates Ca 2π through L-type Ca 2π channels (Schramm et al 1983). In contrast to harmaline, harman and harmine relaxed KCl-induced contraction with higher potencies and interacted with the 1,4-dihydropyridine binding site with higher affinities.…”

Section: Discussionsupporting

confidence: 55%

“…Harmaline, at the concentrations needed to inhibit the smooth muscle contraction, has been reported to inhibit the increase of 45 Ca 2π uptake induced by high K π , noradrenaline and carbachol in rabbit aorta and guinea-pig taenia, indicating an inhibition on Ca 2π channels of vascular and intestinal smooth muscles (Karaki et al 1986). Consistent with this report, the present results show that harmaline relaxes KCl-induced contraction of guinea-pig tracheal smooth muscle, although its relaxation potency is 6.6 times less than that for carbachol.…”

Section: Discussionmentioning

confidence: 99%

“…The vasorelaxant effects of the above-mentioned 4 compounds and other related harmala alkaloids were firstly demonstrated in rabbit isolated aorta by relaxing 65.4 mM K π -and 1 mM noradrenaline-induced sustained contractions with EC 50 (the effective concentration to produce a 50% maximal relaxation) values among 1.3-22.0 mM (Karaki et al 1986). These compounds also relaxed 45.4 mM K π -and 1 mM carbachol-induced contractions of guineapig taenia with EC 50 values among 0.6-43.0 mM (Karaki et al 1986). Earlier studies also indicated that harmine and harmaline inhibited the contractile responses induced by oubain and acetylcholine in guinea-pig ileal smooth muscle (Hider et al 1981a & b).…”

Section: )mentioning

confidence: 99%

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Spasmolytic Effects of Three Harmala Alkaloids onGuinea‐Pig Isolated Trachea

Shi¹,

Liao²,

Chen³

2001

Pharmacology & Toxicology

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The present study examined and compared the spasmolytic effects of 3 harmala alkaloids, harmine, harman, and harmaline, on carbachol-, histamine-, and KCl-induced contractions of guinea-pig isolated tracheal preparations. All 3 compounds relaxed the tracheal preparations contracted by these spasmogens with similar or different EC 50 values, harmine being the most potent one. The cumulative concentration-response curves of all 3 compounds for carbacholinduced contraction were shifted to the right by propranolol (1 mM) pretreatment, indicating the involvement of the activation on the b-adrenoceptors. All 3 compounds shifted the concentration-response curves of carbachol to the right in a parallel manner with the pA 2 values comparable with their relaxation EC 50 values, indicating a competitive antagonism at the muscarinic receptors. Receptor binding assays indicated that all 3 compounds interacted with lung muscarinic receptors (K i Ω11-13 mM), histamine H 1 receptors (K i Ω27-107 mM), and b 2 -adrenoceptors (K i Ω20-51 mM). Therefore, in addition to their actions on receptor-linked and voltage-dependent Ca 2π channels as reported in other types of smooth muscle, the present study suggests that the actions on muscarinic receptors, histamine H 1 receptors, and b 2 -adrenoceptors are also involved in their spasmolytic effects on airway smooth muscles.The harmala alkaloids harmine, harman, harmaline, and harmalol are the psychological active principles from the seeds of Peganum harmala L., which are also found widely in other medicinal plants. Harman is also found endogenously in mammalian tissues (Airaksinen & Kari 1981;Rommelspacher et al. 1991). These harmala alkaloids have a wide spectrum of pharmacological actions in the central nervous system such as tremorogenesis (Poirier et al. 1966;Lutes et al. 1988), hypothermia (Bruinvels & Sourkes 1968), hallucinogenesis (Zetler et al. 1974;Grella et al. 1998), central monoamine oxidase inhibition (Nelson et al. 1979;Fuller et al. 1986;May et al. 1991), convulsive or anticonvulsive actions (Loew et al. 1985) and binding to various receptors including 5-HT receptors and the benzodiazepine binding site of GABA A receptors (Lamarre & Puil 1974;Rommelspacher et al. 1980 Rommelspacher et al. & 1985. In addition, these compounds also have antioxidative (Tse et al. 1991), platelet aggregation inhibitory (Saeed et al. 1993), and immunomodulatory effects (Li 1996). There are also some reports concerning the cardiovascular actions of these harmala alkaloids. For example, it has been reported that harmine reduces systemic arterial blood pressure and total peripheral vascular resistance; harmaline-evoked decreases are frequently followed by a secondary increase; and the effects of harmalol on these two parameters are inconsistent (Aarons et al. 1977). Recently, we reported in vivo cardiovascular effect and in vitro vasorelaxant effect of harman (Shi et al. 2000) and in vitro vasorelaxant effects of harmine, harmaline, and harmalol (Shi et al. 2001). Our results suggest...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Spasmolytic Effects of Three Harmala Alkaloids onGuinea‐Pig Isolated Trachea

Shi¹,

Liao²,

Chen³

2001

Pharmacology & Toxicology

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“…Harmaline, at the concentrations needed to inhibit the smooth muscle contraction, has been reported to inhibit the increase of 45 Ca 2+ uptake induced by high K + , norepinephrine and carbachol in rabbit aorta and guinea pig taenia, indicating an inhibition on Ca 2+ channels of vascular and intestinal smooth muscles (26). Furthermore, the inhibitory effects of harmaline on these smooth muscles were not reversed by Bay K 8644 (26), a dihydropyridine that stimulates Ca 2+ through L-type Ca 2+ channels (27), indicating that the DHP binding site of L-type Ca 2+ channels is not involved.…”

Section: +Ecmentioning

confidence: 99%

Comparative Study on the Vasorelaxant Effects of Three Harmala Alkaloids In Vitro

Shi¹,

Liao²,

Chen

2001

Japanese Journal of Pharmacology

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ABSTRACT-Three psychological active principles from the seeds of Peganum harmala L., harmine, harmaline and harmalol, showed vasorelaxant activities in isolated rat thoracic aorta preparations precontracted by phenylephrine or KCl with rank order of relaxation potency of harmine > harmaline > harmalol. The vasorelaxant effects of harmine and harmaline (but not harmalol) were attenuated by endothelium removal or pretreatment with a nitric oxide (NO) synthase N M -nitro-L-arginine methyl ester. In cultured rat aortic endothelial cells, harmine and harmaline (but not harmalol) increased NO release, which was dependent on the presence of external Ca 2+. In endothelium-denuded preparations, pretreatment of harmine, harmaline or harmalol (3 -30 mM) inhibited phenylephrine-induced contractions in a non-competitive manner. Receptor binding assays indicated that all 3 compounds interacted with cardiac a1-adrenoceptors with comparable affinities (Ki value around 31 -36 mM), but only harmine weakly interacted with the cardiac 1,4-dihydropyridine binding site of L-type Ca 2+ channels (Ki value of 408 mM). Therefore, the present results suggested that the vasorelaxant effects of harmine and harmaline are attributed to their actions on the endothelial cells to release NO and on the vascular smooth muscles to inhibit the contractions induced by the activation of receptor-linked and voltage-dependent Ca 2+ channels. The vasorelaxant effect of harmalol was not endothelium-dependent.

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Chemoinformatic analysis of alkaloids isolated from Peganum genus

Bayazeid

Nasibova

2021

Mol Divers

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Peganum genus is rich with its high phytochemical and botanical variability. Peganum species have been used as sedative, antitumor, analgesics, antidepressant, and other medicinal purposes. The aim of this research is to study the molecular diversity of Peganum genus to shed more lights on the structureactivity relationship of the alkaloids isolated from Peganum genus. All Peganum alkaloids were grouped according to their structure properties. A chemoinformatic approach (Swiss Model) was used to determine the molecular targets of these alkaloids. To visualize the results, R programming language was used to generate hierarchical clustering heatmaps. The results of this study helps researcher to better understanding of the structural-activity relationship of Peganum alkaloids.

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Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles

Cited by 4 publications

References 16 publications

Spasmolytic Effects of Three Harmala Alkaloids onGuinea‐Pig Isolated Trachea

Spasmolytic Effects of Three Harmala Alkaloids onGuinea‐Pig Isolated Trachea

Comparative Study on the Vasorelaxant Effects of Three Harmala Alkaloids In Vitro

Chemoinformatic analysis of alkaloids isolated from Peganum genus

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