Antagonism of Ca2+ and other actions of verapamil in guinea‐pig isolated trachealis

• Published in: British journal of pharmacology 1984-03, Vol.81 (3), p.499-507
• Main Authors: Foster, R.W., Okpalugo, B.I., Small, R.C.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Action Potentials - drug effects; Airway Resistance - drug effects; Animals; Biological and medical sciences; Calcium Channel Blockers; Dinoprostone; Electrophysiology; Female; Guinea Pigs; Histamine - pharmacology; In Vitro Techniques; Male; Medical sciences; Pharmacology. Drug treatments; Potassium Chloride - pharmacology; Prostaglandins E - pharmacology; Respiratory system; Tetraethylammonium; Tetraethylammonium Compounds - pharmacology; Trachea - drug effects; Trachea - metabolism; Verapamil - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1984.tb10103.x

1 In trachealis bathed by a K+‐rich, Ca2+‐free physiological salt solution, calcium chloride (CaCl2) at 0.01 to 10 mmol l−1 evoked concentration‐dependent spasm. Verapamil (0.1 to 10 μmol l−1) was an effective antagonist of CaCl2. 2 Spasm evoked by acetylcholine, histamine, potassium chloride (KCl) and tetraethylammonium (TEA) was studied in trachealis bathed by normal Krebs solution. Verapamil (0.1 to 10 μmol l−1) markedly suppressed spasm evoked by KCl and TEA. In contrast the actions of acetylcholine and histamine were much less affected by verapamil. 3 Spasm evoked by prostaglandin E2 was studied in trachealis bathed by Krebs solution containing indomethacin (2.8 μmol l−1). Verapamil (0.1 to 10 μmol l−1) had little or no effect against prostaglandin E2‐induced spasm. 4 Verapamil (0.1 to 10 μmol l−1) had relatively little effect on the tone of trachealis bathed by normal Krebs solution. In contrast bathing in Krebs solution lacking CaCl2 caused almost complete tone loss. 5 Extracellular electrophysiological recording showed that verapamil (10 μmol l−1) suppressed not only TEA‐evoked spasm but also TEA‐evoked slow waves and spike potentials. Verapamil also abolished the transient period of slow wave activity associated with the spasm evoked by KCl. 6 Intracellular electrophysiological recording showed that TEA‐induced spike activity was resistant to tetrodotoxin (3 μmol l−1). However, verapamil (10 μmol l−1) abolished the tetrodotoxin‐resistant spikes without increasing the resting membrane potential. 7 It is concluded that verapamil suppresses TEA‐ or KCl‐induced spasm, slow waves or spikes by inhibition of Ca2+ influx. Spasm evoked by acetylcholine, histamine and prostaglandin E2 depends on mechanisms for increasing the cytoplasmic concentration of free Ca2+ which are resistant to verapamil. The failure of verapamil markedly to depress tissue tone is consistent with the proposal that tone results from the activity of endogenous prostaglandins.