Inhibitory effects of catecholamines on cholinergically and non-cholinergically mediated contractions of guinea-pig isolated bronchial muscle

Abstract

The actions of catecholamines on the responses evoked by electrical field stimulation or by acetylcholine and substance P in guinea-pig bronchial strip chain have been examined. Electrical field stimulation evoked a biphasic contraction, consisting of a cholinergically-mediated fast contraction followed by a non-cholinergically-mediated slow contraction. All catecholamines tested caused a concentration-dependent reduction in the height of the biphasic contraction, where non-cholinergic contractions were more potently inhibited. The inhibitory effect of isoprenaline was largely prevented by propranolol (2 microM) alone, whereas those of noradrenaline and adrenaline were prevented by treatment with both propranolol (2 microM) and yohimbine (2 microM). The inhibitory effect of dopamine was unaffected either by propranolol (2 microM), yohimbine (2 microM) or haloperidol (10 microM). Submaximal contractions of bronchial muscle evoked by exogenous acetylcholine (2 microM) or substance P (0.2 microM) were also inhibited by catecholamines, except dopamine, but the effects were antagonized by propranolol (2 microM) alone. The results suggest that in guinea-pig isolated bronchial muscle, catecholamines can inhibit both cholinergic and non-cholinergic excitatory neurotransmissions not only by postjunctional beta-adrenoceptors but also by prejunctional alpha 2-adrenoceptors.

Effects of BRL 38227 on neurally‐mediated responses in the guinea‐pig isolated bronchus

“…Moreover, these agonists were more effective than BRL 38227 at producing relaxation of ACh-induced spasm of the bronchial smooth muscle (Figure 4). These findings show good agreement with previous work using ketotifen and isoprenaline (Kamikawa, 1989;Kamikawa & Shimo, 1990) (Mondot et al, 1990), are each thought to cause smooth muscle relaxation by opening K+-channels in the plasmalemma of smooth muscle cells (Bray et al, 1987;Arch et al, 1988;Mondot et al, 1988 (Ashcroft, 1988). At higher concentrations, it has been shown to block an ATP-dependent K+-channel opened by cromakalim in rabbit mesenteric arterial smooth muscle cells (Standen et al, 1989).…”

Effects of two β3‐adrenoceptor agonists, SR 58611A and BRL 37344, and of salbutamol on cholinergic and NANC neural contraction in guinea‐pig main bronchi in vitro

“…Nevertheless, Martin & Collier (1986) could not demonstrate that the P-adrenoceptor agonist, noradrenaline, inhibited the release of acetylcholine from cholinergic nerves in canine airways. Other studies (Kamikawa & Shimo, 1990;Verleden et al, 1991) have also previously demonstrated the inhibitory effects of noradrenaline and P2-adrenoceptor agonists (formoterol, salbutamol) on the EFS-induced NANC contraction in guinea-pig bronchi. Our present study is consistent with a postjunctional mechanism of salbutamol since we observed an inhibitory effect of this compound on cumulative concentration-response curves to acetylcholine, substance P and , the latter compound being a selective agonist of NK2-receptors.…”

“…The effects of salbutamol were abolished or inhibited by both the nonselective P-adrenoceptor antagonist, propranolol, and by the selective ICI 118,551, showing that the effects of salbutamol are due to stimulation of P2-adrenoceptors. The inhibitory effects of P-adrenoceptor agonists on the cholinergic response induced by EFS or vagal stimulation have previously been described for the guinea-pig isolated bronchus (Kamikawa & Shimo, 1990), the canine isolated bronchus (Cabezas et al, 1971;Vermeire & Vanhoutte, 1979;Martin & Collier, 1986;Danser et al, 1987;Ito, 1988) and for human bronchi (Rhoden et al, 1988;Aizawa et al, 1991) and they have been attributed to prejunctional inhibition because P-adrenoceptor agonists were more effective in inhibiting this response than similar contractile responses induced by exogenous acetylcholine (Vermeire & Vanhoutte, 1979;Ito, 1988;Aizawa et al, 1991). Nevertheless, Martin & Collier (1986) could not demonstrate that the P-adrenoceptor agonist, noradrenaline, inhibited the release of acetylcholine from cholinergic nerves in canine airways.…”

β2-Adrenoreceptor immunoreactivity in cardiac ganglia of the guinea pig

“…Their relatively greater thickness, however, favours a contribution by preganglionic and sensory axons. Sensory axons are especially likely candidates, since [32-adrenoreceptor protein and mRNA have been identified by immunohistochemistry and in situ hybridization in dorsal root ganglion neurons (Kloock & Kummer, 1994;Kummer et aI., 1994), and [32-agonists inhibit neuropeptide release from peripheral sensory nerve endings (Kamikawa & Shimo, 1990;Barnes, 1992).…”