Effect of adrenoceptor agonists on striated muscle strips of the canine oesophagus

Abstract

1. Acute psychological stress, which could be related to the release of a large amount of catecholamines, may cause oesophageal motility disorders. Therefore, the aim of our study was to elucidate the influence of adrenoceptor agonists on the striated muscle portion of the oesophagus by use of isolated strips from dogs. 2. Contractions were evoked in isolated striated muscle strips by electrical field stimulation (1 pulse min-1, 1 ms/pulse, submaximal voltage). The effects induced by administration of adrenoceptor agonists alone or in the presence of antagonists were tested to determine the nature of the adrenoceptors on this muscle preparation. 3. The administration of both the natural adrenoceptor agonists, adrenaline and noradrenaline, and the synthetic beta-adrenoceptor agonists, isoprenaline (beta 1 + beta 2), dobutamine (beta 1) or ritodrine (beta 2), enhanced the amplitude of the contractions induced by electrical stimulation in a concentration-dependent manner. The maximum responses were 82.6 (adrenaline), 66.2 (noradrenaline), 86.2 (isoprenaline), 34.6 (dobutamine) and 80.8% (ritodrine). The EC20 values obtained were respectively 2 nM, 0.2 microM, 0.91 nM, 3 microM and 80 nM. The administration of the alpha 1-adrenoceptor agonist, phenylephrine, also enhanced the contractile response in a concentration-dependent manner (EC20 value = 0.3 microM) and the maximum response was 64.6%, but the administration of the alpha 2-adrenoceptor agonist, clonidine, did not influence the contractile response. These data suggest the involvement of beta 2- and possibly alpha 1-adrenoceptors in the responses of these adrenoceptor agonists. 4 The selective P2-adrenoceptor antagonist ICI 118551 (3-100nM) shifted the concentration-effect curves for noradrenaline, phenylephrine and ritodrine to the right in a concentration-dependent manner.ICI 118551 (3 nM) also shifted the concentration-effect curves for adrenaline and isoprenaline to the right, but increasing the concentration of ICI 118551 did not cause any further antagonist activity until a concentration of 100 nM, when a further rightward shift was obtained.5. The selective alpha 1-adrenoceptor antagonist, prazosin (30-300 nM), did not affect the increased contractile responses induced by adrenaline, noradrenaline, phenylephrine, isoprenaline or ritodrine.6. In conclusion, it appears that beta2-adrenoceptors are present in the striated muscle portion of the canine oesophagus, where they mediate an enhancement of contractile responses evoked by electrical stimulation. The alpha l-agonist, phenylephrine, appears to interact with beta2-adrenoceptors on this preparation.beta 3-Adrenoceptors have already been demonstrated in smooth muscle from various parts of the gastrointestinal tract, and our study does not exclude the possibility that there is an additional population of beta 3-receptors in the canine striated muscle part of the oesophagus.