Effects of Noradrenaline and Isoprenaline on the Electrical and Mechanical Activities of Guinea Pig Depolarized Taenia Coli

Abstract

Summary The effects of noradrenaline and isoprenaline on the electrical and mechanical properties of depolarized smooth muscle of the guinea pig taenia coli were investigated by the double sucrose gap method. 1. Noradrenaline (10-7-10-5 g/ml) decreased the membrane resistance at any given concentration of excess K ion. When increased K ion concentration accelerated the spike discharges, noradrenaline blocked the spike generation as a result of the consequent reduction in membrane resistance, thus causing relaxation. When the excess K ion depolarized the muscle and no spike generation was observed due to depolarization block, noradrenaline no longer caused relaxation of the tissue. Phentolamine (10-5 g/ml) completely blocked the effect of noradrenaline. 2. Acetylcholine (10-5 g/ml) and noradrenaline (10-5 g/ml) reduced the membrane resistance and blocked the spike generation to the same extent in 59 mm K-Krebs solution. However, acetylcholine enhanced and noradrenaline reduced the contraction. 3. Isoprenaline (10-7-10-5 g/ml) reduced the tonic response of the contraction without any marked changes in the membrane resistance, membrane potential and membrane activity, at any given concentration of excess K ion. 4. Isoprenaline (10-7-10-5 g/ml) did not reduce the tonic response evoked by excess K ion in Na-free solution. It is suggested that external Na ion might be important for the reduction of the internal free Ca ion concentration. In the Cl-deficient (C6H5S0O3), excess K+ condition, isoprenaline again had no effect on the depolarized muscle. 5. When Ca ion in the excess K-Krebs solution was replaced by Sr and Ba ions, the effect of isoprenaline on the tonic response was markedly suppressed. 6. Ouabain (10-5-10-4 g/ml) reduced the membrane resistance and the tonic response evoked by excess K+ (below 59 mm) solution. In

Evidence for the existence of ‘atypical’β‐adrenoceptors (β3‐adrenoceptors) mediating relaxation in the rat distal colon in vitro

“…Inhibitory postjunctional a1-adrenoceptors have previously been shown to exist in the rat distal colon (Dettmar et al, 1986a) and the failure to show their presence in the present study is probably related to the KCI-induced depolarization, since cx-adrenoceptor-mediated inhibitory effects in intestinal smooth muscle involve abolition of spontaneous spike discharge and hyperpolarization (Bulbring, 1954;1957) and are not seen if the tissue is depolarized sufficiently to block spike generation (Magaribuchi & Kuriyama, 1972 The relaxations to the catecholamines were also elicited in the presence of propranolol (1 pM), conditions under which one would assume that classical f-adrenoceptors had been blocked. Propranolol did produce a shift of the isoprenaline CRC but the antagonism was non-competitive (slope of Schild plot less than unity) and weak with an apparent pA2 of 6.57 compared with 8.2-8.8 for classical 01J-adrenoceptors mediating atrial stimulation and 8.3-8.6 for 82-adrenoceptors mediating tracheal relaxation .…”

Adrenoceptors mediating relaxation to catecholamines in rat isolated jejunum

“…Bond & Clarke (1988) further experiments to analyse these small shifts further but it seems likely that they were produced by blockade of classical P-adrenoceptors since (i) propranolol itself has been shown to produce similar shifts in rat colon and fundus (McLaughlin & MacDonald, 1990; and (ii) o-adrenoceptor mediated inhibitory effects in smooth muscle involve abolition of spontaneous spike discharge and hyperpolarization (Bulbring, 1954;1957) and are not seen if the tissue is depolarized sufficiently to block spike generation (Magaribuchi & Kuriyama, 1972). The relative potencies of the catecholamines and BRL 37344 in the presence of prazosin and propranolol, with BRL 37344 becoming more potent than isoprenaline, are similar to those obtained by Bond & Clarke (1988) at the atypical P-adrenoceptors in guinea-pig ileum.…”

Beta‐adrenergic inhibition of bovine mesenteric lymphatics.

“…Thus f-inhibition can be associated with anything from depolarization in rat portal vein (Johansson, Jonsson, Axelsson & Wahlstrom, 1967;Ljung, Isaksson & Johansson, 1975), no change in membrane potential in taenia coli (Biulbring & Tomita, 1969) to a marked hyperpolarization in rat myometrium (Diamond & Marshall, 1969;Magaribuchi & Osa, 1971;Kroeger & Marshall, 1973). Smooth muscle depolarized in high-K+ solution is still relaxed by isoprenaline (Schild, 1967;Diamond & Marshall, 1969;Magaribuchi & Kuriyama, 1972) and this is also true of lymphatic smooth muscle (unpublished observations) indicating that a membrane potential change is not essential for the fl-inhibitory effect. However it may be part of the same inhibitory process.…”