Effects of Clonidine on Excitation-Contraction in Guinea-Pig Taenia Coli

Abstract

Among the effects of clonidine [St 155, 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride], those on the cardiovascular system have received considerable attention.Clonidine induces a biphasic change in blood pressure, consisting of initial brief hypertension and subsequent long-lasting hypotension (1). The initial hypertension has been explained by a sympathomimetic action of this drug and the subsequent hypotension by some centrally mediated repression of the sympathetic tone (2-5).<BR>The isolated preparation of taenia coil is an excellent material to study sympathomimetic and parasympathomimetic actions of drugs, responding to the former with inhibition and to the latter with excitation (6,7). The present paper reports the effects of clonidine on the excitation and contraction of taenia coll. The knowledge obtained with this material will be useful to interpret the drug actions on smooth muscle in general. MATERIAL AND METHODSAll experiments were performed with taenia coli isolated from guinea-pig. The animal was sacrificed by a blow on the head. A piece of taenia coli, about 2 cm long in situ, was dissected free from the underlying tissue after the abdomen was opened and the colon exposed. The sucrose-gap method invented by Sldmpfli (8) was used to record the electrical activity. The recording chamber employed in the present study was modified according to Washizu (9). Potential changes and isometric contractions were simulta neously recorded with a pen-writing oscillograph.The Tyrode solution used was of the following composition (mM): NaCI, 137; KCI, 4; MgCI.,, 1.2; CaCl.,, 2.5; NaHCO, 12; NaHPO_,, 0.4; and glucose, 11. The solution with 20 or 80 mM K+ level was prepared by increasing KCI in an appropriate amount and by reducing equimolar NaCl without changing the concentrations of other salts. The Tyrode or test solution applied to the preparation was warmed up to 37 L. and aerated with a gas mixture of 95°; 0, and 5°" CO,. The drugs used were as follows: clonidine hydrochloride (C.H. Boehringer Sohn), atropine sulfate (Wako) and tetrodotoxin (Sankyo). These drugs were applied to the preparation by being freshly dissolved in the bath saline. RESULTS1. Effects of c'lnaidiac na spike dischca'gc rate contraction C lonlChne enhanced the rate and alllplltude of spontaneous spike discharge of taenia