Modification of alpha 1-receptor-operated channels by mebeverine in smooth muscle cells of guinea-pig taenia caeci.

Changes in the potential and contractility of smooth muscle cells of guinea-pig taenia caeci were measured (22 degrees C) in order to investigate the effect of mebeverine, a derivative of beta-phenylethylamine, on alpha 1-receptor-operated ion channels in particular. Mebeverine (6 X 10(-6) M) showed atropine-like properties by shifting to the right the concentration-response curve obtained with carbachol. Hyperpolarization and cessation of spike activity of the muscle cells, accompanied by an increased amplitude of the electrotonic potential were observed in the presence of mebeverine (6 X 10(-5] after block of the alpha 2-, beta- and muscarinic receptors. This effect of mebeverine was not observed in low-sodium solution (23.8 mM), suggesting that mebeverine decreased sodium permeability. The alpha 1-receptor-induced hyperpolarization caused by adrenaline (3 X 10(-6) M) in the presence of mebeverine declined after reaching an initial maximum. The hyperpolarization induced by a second addition of adrenaline to the preparation was decreased and sustained in the presence of mebeverine, while the decrease of the electrotonic potential evoked during the alpha 1 response was less pronounced. The transient hyperpolarization representing the alpha 1 response in the absence of extracellular calcium developed more slowly in the presence of mebeverine, the area of the response being constant. When the experiment was continued in calcium-free solution after a short exposure to calcium-containing Krebs solution still in the presence of mebeverine, the alpha 1-receptor-induced hyperpolarization was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)