Contributions of β-Adrenoceptor Subtypes to Responses to Isoprenaline in Rat Isolated Distal Colon

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Abstract
The effects of the non-selective β-adrenoceptor antagonist propranolol and the β1 and β2-adrenoceptor-selective antagonists, respectively CGP 20712A (((±)-[2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]-2-propanol hydrochloride)) and ICI 118,551 ((erythro(±)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol-hydrochloride)), on isoprenaline-induced inhibition of methacholine contractions in rat distal colon were investigated to determine the contributions of β-adrenoceptor subtypes to relaxation of smooth muscle. Longitudinal segments of rat distal colon were suspended in Krebs solution at 37°C for isometric recording. The Krebs solution contained EDTA (30 μm), ascorbic acid (30 μm) and prazosin (0·1 μm) 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 μm. Larger shifts were produced by 0·3 μm (13-fold) and 1 μm (20-fold). CGP 20712A produced a small (3–5-fold) significant shift at 0·03–1 μm. ICI 118,551 produced small non-significant shifts (2–3-fold) at 0·03–1 μm. A combination of ICI 118,551 (0·3 μm) and CGP 20712A (0·1 μm) 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 μm propranolol (20-fold). The effects of propranolol appear to be due mainly to a combination of β1 and β2-adrenoceptor blockade, although an additional action of propranolol at β3-adrenoceptors is likely.