Effects of diltiazem and other Ca2+ antagonists on guinea-pig tracheal muscle

Cerrina, Jacques; Advenier, C.; Renier, Annick; Floch, Anne; Duroux, P

doi:10.1016/0014-2999(83)90413-2

Cited by 43 publications

(18 citation statements)

References 18 publications

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“…Further evidence to this effect is provided by the observation (Cerrina et al, 1983;Cheng & Townley, 1983;Foster et al, 1984) that organic inhibitors of the voltage-operated Ca2+ channel (i.e. diltiazem, nicardipine, nifedipine and verapamil) can markedly depress cumulative concentration-tension curves for potassium chloride and tetraethylammonium without depressing such curves for acetylcholine and histamine.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is possible that subsequent maintenance of that tension does require some Ca2+ influx, for organic calcium antagonists are able to reduce established spasm in trachealis treated with muscarinic agonists or histamine (Cerrina et al, 1983;Cheng & Townley, 1983;Ahmed et al, 1983;Foster & Small, unpublished observations). In view of this we propose that, for spasmogenic responses to acetylcholine or histamine, release of Ca2+ from intracellular sites of sequestration alone is sufficient for the development of tension but the subsequent maintenance of the developed tension may also involve Ca2+ influx through channels sensitive to the organic calcium antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…An ability of acetylcholine and histamine to depolarize guinea-pig trachealis might suggest that these agents should activate voltage-operated channels (Bolton, 1979) which admit Ca2+ into the smooth muscle cells. However, the resistance of acetylcholine-or histamine-induced tension development to inhibitors of Ca2+ influx (Cerrina et al, 1983;Cheng & Townley, 1983;Foster et al, 1984) suggests that Ca2+ entry through voltage-operated channels cannot be a major underlying mechanism. Acetylcholine might instead act to release Ca2+ from intracellular sites of sequestration (Creese & Denborough, 1981;Cerrina et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

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Some features of the spasmogenic actions of acetylcholine and histamine in guinea‐pig isolated trachealis

Ahmed

Foster

Small

et al. 1984

British J Pharmacology

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Intracellular electrophysiological recording showed that acetylcholine (1 μmol l−1) and histamine (2 μmol l−1) depolarized trachealis cells and often increased the frequency of slow waves. Higher concentrations of these agents caused greater depolarization and abolition of slow waves. Marked depolarization was often associated with the appearance of electrical ‘noise’. These electrical phenomena were accompanied by tonic tension development in a contiguous segment of trachea. Electrical ‘noise’ and tension evoked by high concentrations of acetylcholine or histamine could be dissipated by washing the agonist from the tissue. Acetylcholine‐induced ‘noise’ was resistant to tetrodotoxin (3 μmol l−1) and to hexamethonium (1 mmol l−1). Neither acetylcholine (10–1,000 μmoll−1) nor histamine (2–200 μmol l−1) increased the lanthanum‐resistant calcium fraction of muscle‐containing strips of trachea. It is concluded that, while developing tension under the influence of acetylcholine or histamine, trachealis cells depolarize markedly but there is relatively little cellular influx of Ca2+.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Some features of the spasmogenic actions of acetylcholine and histamine in guinea‐pig isolated trachealis

Ahmed

Foster

Small

et al. 1984

British J Pharmacology

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“…Calcium movements through potential-operated channels (POC) have been demonstrated in guinea-pig airways muscle both directly, by measuring 45Ca2+ uptake by the lanthanum method (Foster et al, 1983b;Allen et al, 1985), and indirectly, by using Ca2+ in a K+-enriched solution as described by Godfraind et al (1978) (Cerrina et al, 1983;Advenier et al, 1984); by investigating the effects of agents, such as potassium chloride, tetraethylammonium (TEA) or barium chloride, which tend to open POC (Cerrina etal., 1983;Foster et al, 1983a,b;Advenier et al, 1984); or by studying the effects of dihydropyridines that stimulate (Bay K 8644) (Allen et al, 1985) or antagonize (nifedipine, nicardipine or dazopidine) (Cerrina et al, 1983;Advenier et al, 1984) Ca2+ transport across the cell membrane. These studies have shown that KCl, TEA and BaCl2 contract the guinea-pig isolated trachea and that this effect is inhibited specifically by organic calcium antagonists, notably dihydropyridine derivatives.…”

Section: Discussionmentioning

confidence: 99%

“…These derivatives also inhibit specifically the contractile effects of Ca2" in K+-enriched medium (Cerrina et al, 1983;Advenier et al, 1984). In this respect, the guinea-pig isolated trachea reacts to calcium antagonists very much like different types of vascular segments, such as rat aorta and mesenteric arteries, rabbit aorta and basilar artery, or dog coronary and mesenteric arteries (Advenier et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea‐pig isolated trachea

Advenier¹,

Naline²,

Renier³

1986

British J Pharmacology

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1 The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potentialoperated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca2" on human isolated bronchial strips and the results were compared to those obtained on guinea-pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K+-enriched medium and in the presence of Ca2" 0.03 mM were investigated.2 In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC50 of acetylcholine or histamine on the human bronchus, but in concentrations of 10-7-10-6M it potentiated the effects of KC1 on that preparation. It did not modify the EC50 of acetylcholine, histamine or KCl on the guinea-pig trachea. 3 In Ca2+-free Krebs medium with additional K+ (30 mM), Ca2+ concentration-response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 ± 0.1 1 and 0.72 ± 0.16 log units respectively with Bay K 8644 10-8 and 10-7 M on human bronchus (n = 4) and 0.67 ± 0.16 and 1.06 ± 0.19 log units respectively with Bay K 8644 10-7 and 10-6 M on the guinea-pig trachea (n = 5).4 In Krebs medium with Ca2`0.03 mM and K+ 30 mM, Bay K 8644 (10-8 to 10-6 M) contracted both the human bronchus and the guinea-pig isolated trachea. This effect was competitively antagonized by nicardipine. 5These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca2+ influx through potential-operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea-pig isolated trachea to Bay K 8644.

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Comparative evaluation of the relaxant effects of MDL‐257, its metabolits, and some related compounds on guinea pig tracheal cylindrical segments

Abdallah¹,

Burnell²,

Cregge³

1986

Drug Development Research

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Abdallah, A.H., J.W. Burnell, and R.J. Cregge: Comparative evaluation of the relaxant effects of MDL-257, its metabolites, and some related compounds on guinea pig tracheal cylindrical segments. Drug Dev. Res. 7:185-193, 1986. The smooth muscle relaxant activities of pyridazine], a new, nonsympathomimetic bronchodilator, its metabolites (in man and rats), and some related compounds were compared to that of aminophylline in guinea pig tracheal cylindrical segments. The lC50 of MDL-257 against KCI-, histamine-, acetylcholine, and 5-hydroxytryptamine-induced contractions were 5.2 x 5.3 x 9.1 x and 1.4 x l o w 5 M, respectively. The relaxant activity of aminophylline was equal to that of MDL-257 against all of the spasmogens studied. Dihydroxy substitution on the piperidine ring of MDL-257 reduced its relaxant activity against KCI, histamine, and 5-hydroxytryptamine 25-43-fold and its activity against acetylcholine was almost abolished. The monohydroxy and the amino alcohol metabolites of MDL-257 were two to 20 times less potent than the parent compound and their activities against acetylcholine-induced contractions were minimal. The acidic metabolites of MDL-257 exhibited very weak activity against all of the spasmogens tested.

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Effects of diltiazem and other Ca2+ antagonists on guinea-pig tracheal muscle

Cited by 43 publications

References 18 publications

Some features of the spasmogenic actions of acetylcholine and histamine in guinea‐pig isolated trachealis

Some features of the spasmogenic actions of acetylcholine and histamine in guinea‐pig isolated trachealis

Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea‐pig isolated trachea

Comparative evaluation of the relaxant effects of MDL‐257, its metabolits, and some related compounds on guinea pig tracheal cylindrical segments

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