Inhibition of field stimulation‐evoked relaxations in rat oesophageal smooth muscle by the calcium antagonist PN 200–110

H. I. Akbarali, D. Bieger, Christopher Triggle

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The inhibitory effects of the 1,4‐dihydropyridine calcium channel antagonist, PN 200–110 (isradipine), on field stimulation‐evoked tetrodotoxin (TTX)‐sensitive and‐insensitive relaxations were studied in rat oesophageal smooth muscle of the tunica muscularis mucosae. The TTX‐insensitive relaxation was inhibited by PN 200–110 in a stereoselective manner with the (+)−(S)‐isomer displaying a 1000 fold greater inhibitory potency than the (—)−(R) isomer. A similar potency was noted for inhibition of high K+‐evoked contractions. TTX‐sensitive relaxations evoked by field stimulation and contractions elicited by the muscarinic cholinoceptor agonist, cis‐2‐methyl‐4‐dimethylamino‐methyl‐1,3‐dioxolane methiodide (cis‐dioxolane) were considerably less sensitive to inhibition by PN 200–110, although, again, stereoselectivity for PN 200–110 was apparent. Pretreatment with (+)−(S)‐PN 200–110 resulted in a non‐competitive displacement of the Ca2+ concentration‐response curves obtained in the presence of either isotonic 50 mm KCl or cis‐dioxolane. The effect of K+ was 10 fold more sensitive than that of cis‐dioxolane. The potency rank orders for inhibition of TTX‐insensitive field stimulation‐evoked relaxations and K+‐mediated contractions in a series of calcium channel antagonists were closely correlated; (+)−(S)‐PN 200–110 showing highest potency followed by nifedipine, verapamil, diltiazem, (—)−(R)‐PN 200–110. It is concluded that TTX‐insensitive relaxations are dependent upon an influx of extracellular Ca2+ through potential‐operated calcium channels. 1988 British Pharmacological Society

Original languageEnglish
Pages (from-to)512-518
Number of pages7
JournalBritish Journal of Pharmacology
Volume95
Issue number2
DOIs
Publication statusPublished - 1988
Externally publishedYes

Fingerprint

Calcium Channel Blockers
Smooth Muscle
Isradipine
Calcium
Muscarinic Agonists
Diltiazem
Tetrodotoxin
Cholinergic Receptors
Calcium Channels
Nifedipine
Verapamil
Mucous Membrane

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of field stimulation‐evoked relaxations in rat oesophageal smooth muscle by the calcium antagonist PN 200–110. / Akbarali, H. I.; Bieger, D.; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 95, No. 2, 1988, p. 512-518.

Research output: Contribution to journalArticle

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abstract = "The inhibitory effects of the 1,4‐dihydropyridine calcium channel antagonist, PN 200–110 (isradipine), on field stimulation‐evoked tetrodotoxin (TTX)‐sensitive and‐insensitive relaxations were studied in rat oesophageal smooth muscle of the tunica muscularis mucosae. The TTX‐insensitive relaxation was inhibited by PN 200–110 in a stereoselective manner with the (+)−(S)‐isomer displaying a 1000 fold greater inhibitory potency than the (—)−(R) isomer. A similar potency was noted for inhibition of high K+‐evoked contractions. TTX‐sensitive relaxations evoked by field stimulation and contractions elicited by the muscarinic cholinoceptor agonist, cis‐2‐methyl‐4‐dimethylamino‐methyl‐1,3‐dioxolane methiodide (cis‐dioxolane) were considerably less sensitive to inhibition by PN 200–110, although, again, stereoselectivity for PN 200–110 was apparent. Pretreatment with (+)−(S)‐PN 200–110 resulted in a non‐competitive displacement of the Ca2+ concentration‐response curves obtained in the presence of either isotonic 50 mm KCl or cis‐dioxolane. The effect of K+ was 10 fold more sensitive than that of cis‐dioxolane. The potency rank orders for inhibition of TTX‐insensitive field stimulation‐evoked relaxations and K+‐mediated contractions in a series of calcium channel antagonists were closely correlated; (+)−(S)‐PN 200–110 showing highest potency followed by nifedipine, verapamil, diltiazem, (—)−(R)‐PN 200–110. It is concluded that TTX‐insensitive relaxations are dependent upon an influx of extracellular Ca2+ through potential‐operated calcium channels. 1988 British Pharmacological Society",
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