Inhibition of field stimulation-evoked relaxations in rat oesophageal smooth muscle by the calcium antagonist PN 200-110 Academic Article uri icon

Overview

MeSH Major

  • Calcium Channel Blockers
  • Muscle, Smooth
  • Oxadiazoles

abstract

  • 1. 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. 2. 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. 3. 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 (cisdioxolane) were considerably less sensitive to inhibition by PN 200-110, although, again, stereoselectivity for PN 200-110 was apparent. 4. 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 cisdioxolane. The effect of K+ was 10 fold more sensitive than that of cis-dioxolane. 5. 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. 6. It is concluded that TTX-insensitive relaxations are dependent upon an influx of extracellular Ca2+ through potential-operated calcium channels.

publication date

  • January 1988

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1854195

PubMed ID

  • 2976289

Additional Document Info

start page

  • 512

end page

  • 8

volume

  • 95

number

  • 2