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  • Title: Smooth muscle relaxation and inhibition of responses to pinacidil and cromakalim induced by phentolamine in guinea-pig isolated trachea.
    Author: Bang L, Nielsen-Kudsk JE.
    Journal: Eur J Pharmacol; 1992 Feb 11; 211(2):235-41. PubMed ID: 1612110.
    Abstract:
    A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation when the tone was induced by histamine, carbachol, 30 mM K+ or 124 mM K+. Relaxant EC50 values ranged from 8 to 50 microM with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F2 alpha (PGF2 alpha) or leukotriene C4 (LTC4). At a concentration of 100 microM the alpha 2-adrenoceptor blocker, yohimbine, produced minor inhibition of spasmogen-induced tone, whereas the alpha 1-adrenoceptor blocker prazosin (up to 10 microM) had no inhibitory effects in the trachealis. Propranolol (1 microM), prazosin (1 microM), yohimbine (100 microM), tetrodotoxin (3 microM), glibenclamide (10 microM), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100 microM), dipyridamole (3 microM) or methylene blue (100 microM) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF2 alpha or LTC4, phentolamine (1, 10 and 100 microM) antagonized the relaxant action of the K+ channel openers, pinacidil and cromakalim. The concentration-relaxation curves for pinacidil were shifted 30-fold to the right without change in the maximal effects, whereas the maximal cromakalim-induced relaxant responses were markedly suppressed by phentolamine.
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