The effects of the dihydropyridine Bay K 8644 in guinea-pig isolated trachealis.

Abstract

In trachea bathed by Krebs solution containing indomethacin 0.8 mumol l-1, Bay K 8644 (0.01-1 mumol l-1) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol l-1 potassium chloride (KCl) to the Krebs solution. Bay K 8644 (1 mumol l-1) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine. Bay K 8644 (1 mumol l-1) caused a small potentiation of the effect of calcium chloride (CaCl2) tested in trachea bathed by a K+-rich, Ca2+-free, MOPS-buffered physiological salt solution. Organic inhibitors of calcium influx such as nifedipine (0.1 mumol l-1), verapamil (1 mumol l-1) or diltiazem (10 mumol l-1) each caused marked depression of concentration-effect curves to KCl. Bay K 8644 (0.01-1 mumol l-1) provided concentration-dependent protection against this effect in all three cases. Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 mumol l-1) was able to promote the cellular influx of Ca2+. Intracellular electrophysiological recording showed that Bay K 8644 (1 mumol l-1) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 mumol l-1 nifedipine. The ability of Bay K 8644 to promote Ca2+ influx and its ability to protect against the effects of several structurally-unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage-operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.

• Authors: S L Allen, R W Foster, R C Small, R Towart
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 86 Issue 1 Pg. 171-80 (Sep 1985) ISSN: 0007-1188 [Print] England
• PMID: 2413935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Tetraethylammonium Compounds
• Tetraethylammonium
• Potassium Chloride
• Lanthanum
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Histamine
• Nifedipine
• Calcium Chloride
• Acetylcholine

Topics

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Acetylcholine (pharmacology)
• Animals
• Calcium Channel Blockers (pharmacology)
• Calcium Chloride (pharmacology)
• Electrophysiology
• Female
• Guinea Pigs
• Histamine (pharmacology)
• In Vitro Techniques
• Lanthanum (pharmacology)
• Male
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects)
• Nifedipine (analogs & derivatives, pharmacology)
• Potassium Chloride (pharmacology)
• Tetraethylammonium
• Tetraethylammonium Compounds (pharmacology)
• Trachea (drug effects)