Effect of Calcium Antagonists in Experimental Asthma

Weiss, Earle B.; Markowicz, Jeffrey; Barbero, Linda

doi:10.1111/j.1398-9995.1982.tb02334.x

Cited by 13 publications

(4 citation statements)

References 10 publications

(5 reference statements)

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“…Even though they are weak in blocking the OA-induced contraction in the tracheal smooth muscle, all of them showed a direct relaxing activity on that tissue. Other authors have also demonstrated similar effects on respiratory smooth muscle in-vitro by diltiazem (Nagao et al 1981), by verapamil (Eberlin et al 1982;Weiss et al 1982) and by nifedipine (Drazen et al 1983). Thecontractile activity of respiratory smooth muscle depends on the intracellular calcium provision (Coburn 1977).…”

Section: Discussionmentioning

confidence: 74%

Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity

Ayala

Aleixandre

Mora

1988

Journal of Pharmacy and Pharmacology

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The effect of the calcium antagonists, verapamil, nicardipine and diltiazem, the two cromones, disodium cromoglycate and SM-857 (11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid), and the anthelmintic, diethylcarbamazine citrate, have been compared on the ovalbumin (OA)-induced contraction of the isolated trachea and longitudinal muscle-myenteric plexus (LM-MP) from sensitized guinea-pigs. The calcium antagonists prevented the OA-induced contractions in LM-MP and to a lesser degree the OA-induced contractions in trachea. Similar doses of SM-857 protected both tissues but neither cromoglycate (10(-5)M) nor diethylcarbamazine (10(-5)M) affected these contractions. The OA-induced contraction in trachea had a tonic phase that was not present in the LM-MP response. Only the calcium antagonists succeeded in relaxing this OA tonic component, diltiazem being the more potent. These results unmask different mechanisms of drug action on immediate hypersensitivity and specific sensibilities, depending on the kind of tissue.

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Section: Discussionmentioning

confidence: 74%

Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity

Ayala

Aleixandre

Mora

1988

Journal of Pharmacy and Pharmacology

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“…The results of these trials have thusfar yielded equivocal results [6,7] and there is some uncertainty as to what the mechanism of the beneficial drug-induced bronchodilation might be in asthma. Calcium antagonists either have no ability to block antigen-induced mast-cell or basophil release of histamine, leukotrienes or other inflammatory mediators under in-vitro conditions [8,9,10], or else the blockade requires very high concentrations i.e., 10 -4 M [11,12]. Similarly, a direct bronchodilation caused by these agents in the absence of mediator-induced bronchospasm apparently either does not occur [4,13], or occurs only at high in-vitro concentrations [14].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, a direct bronchodilation caused by these agents in the absence of mediator-induced bronchospasm apparently either does not occur [4,13], or occurs only at high in-vitro concentrations [14]. On the other hand, numerous studies have shown that relatively low concentrations of the calcium antagonists can interfere with vascular and intestinal smooth muscle contractions induced by a variety of autonomic agonists [15] and can inhibit the response of respiratory smooth muscle to diverse inflammatory mediators, including histamine, acetylcholine (ACH) and the leukotrienes [13,14,16] and to various antigens [9,10,13]. Hence, a key mechamsm underlying the effective use of these agents in immune-induced disorders of smooth muscle would seem to be effective blockade of the musculotropic effects of inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

Relative activities of three calcium channel antagonists on histamine, acetylcholine and antigen-induced contractions of guinea pig ileum

Ingenito

1985

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The molar concentrations of verapamil, diltiazem, nifedipine, tripelennamine and atropine necessary to block histamine, acetylcholine (ACH) and ovalbumin-induced contractions of the isolated guinea pig ileum were compared. The calcium blockers inhibited ovalbumin contractions in previously sensitized ilea at lower concentrations than those required to block the phasic component of histamine and ACH contractions. These compounds were, however, more active in blocking the tonic phase of histamine and ACH concentrations than ovalbumin contractions. Tripelennamine was almost as active against ovalbumin contractions as it was against histamine concentrations, while atropine was inactive against ovalbumin. The results are interpreted as being supportive of continued efforts to develop calcium channel antagonists which selectively block the smooth muscle effects of inflammatory mediators.

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“…Calcium antagonists have been reported to exert beneficial (protective) effects in exercise-induced asthma [11 14]. The effects of Ca++-entry blockers on antigen-, histamine-, PGF2~-and methacholine-induced bronchoconstriction in man and animals are highly variable and somewhat controversial [15][16][17][18][19][20][21][22][23][24][25][26][27]38]. Some of the factors that may be responsible for the inconsistent effects of Ca++-channel blockers in immediate hypersensitivity reactions have been outlined in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of calcium channels in mast cells and basophils and the possible relevance to pathophysiology of lung diseases: A review

Chand

Diamantis

et al. 1986

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Calcium plays a critical role in the formation and secretion of a wide variety of chemical mediators. Calcium slow-channel blockers, e.g. nifedipine and verapamil, have been shown to inhibit the synthesis of SRS (SRS-A, leukotrienes) in human and guinea pig lung tissue, thromboxane A2 formation in rat lung and platelet activating factor in human neutrophils. Verapamil and nifedipine also prevent the release of lysosomal enzymes from rabbit and human polymorphonuclear neutrophils. Calcium-channel blockers produce variable inhibitory effects on allergic and nonallergic histamine secretion. Ca++-entry blockers also inhibit the Ca++ uptake (influx) into mast cells. Many of these inhibitory effects of Ca++ antagonists are antagonized by an increased extracellular Ca++ ion concentration. The magnitude of the inhibitory influences of Ca++-channel blockers on allergic and nonallergic release of chemical mediators appears to depend on the cell source, species, nature and the concentration of the secretory stimuli as well as on the composition and pH of buffers and the concentration of Ca++-entry blockers used. The data summarized in this review suggest the existence of a functional heterogeneity of Ca++ channels in leukocytes, mast cells and basophils. Interference with the Ca++-dependent steps involved in the formation and/or release of chemical mediators appears to be the primary mode of action for Ca++-channel blockers in these cells. The differential effects of Ca++ antagonists on Ca++-dependent activation of phospholipase A2,5-lipoxygenase, and calmodulin (or other intracellular Ca++-binding proteins) in different cell types (mast cells, basophils, leukocytes, lung tissue, etc.) may explain the variation of their effectiveness in inhibiting the synthesis/release of chemical mediators and antagonizing bronchoconstriction in response to diverse stimuli. During the process of hypersensitization and in immediate hypersensitivity diseases, Ca++ homeostasis (uptake, mobilization, distribution, relocation, etc.) may be altered in leukocytes (mast cells, basophils) and lung tissues. The altered Ca++ homeostasis could be responsible for the induction of airway hyperreactivity in asthmatics and for hyperreleasability of chemical mediators from leukocytes, mast cells and other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of Calcium Antagonists in Experimental Asthma

Cited by 13 publications

References 10 publications

Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity

Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity

Relative activities of three calcium channel antagonists on histamine, acetylcholine and antigen-induced contractions of guinea pig ileum

Heterogeneity of calcium channels in mast cells and basophils and the possible relevance to pathophysiology of lung diseases: A review

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