Contributions of beta-adrenoceptor subtypes to responses to isoprenaline in rat isolated distal colon.

The effects of the non-selective beta-adrenoceptor antagonist propranolol and the beta 1- and beta 2-adrenoceptor-selective antagonists, respectively CGP 20712A (((+/-)-[2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-meth yl-4- trifluoromethyl-2-imidazolyl)-phenoxy]-2-propanol hydrochloride)) and ICI 118,551 ((erythro(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol- hydrochloride)), on isoprenaline-induced inhibition of methacholine contractions in rat distal colon were investigated to determine the contributions of beta-adrenoceptor subtypes to relaxation of smooth muscle. Longitudinal segments of rat distal colon were suspended in Krebs solution at 37 degrees C for isometric recording. The Krebs solution contained EDTA (30 microM), ascorbic acid (30 microM) and prazosin (0.1 microM) and was gassed with 95% O2-5% CO2. Isoprenaline produced a concentration-dependent inhibition of methacholine-induced contractions. Propranolol produced a small (4-6-fold) significant shift of the isoprenaline concentration-response curve at 0.003-0.01 microM. Larger shifts were produced by 0.3 microM (13-fold) and 1 microM (20-fold). CGP 20712A produced a small (3-5-fold) significant shift at 0.03-1 microM. ICI 118,551 produced small non-significant shifts (2-3-fold) at 0.03-1 microM. A combination of ICI 118,551 (0.3 microM) and CGP 20712A (0.1 microM) produced a 13-fold shift, a significantly greater shift than expected from the individual shifts. The shift produced by the combination of antagonists was slightly less than that produced by 1 microM propranolol (20-fold).(ABSTRACT TRUNCATED AT 250 WORDS)