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Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation

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Summary

  1. 1.

    The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon.

  2. 2.

    The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine > noradrenaline > methoxamine > isoprenaline for the inhibition of peristalsis and isoprenaline > noradrenaline > methoxamine > clonidine for the relaxation of circular muscle.

  3. 3.

    Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both α and β receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release.

  4. 4.

    Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs.

  5. 5.

    Our results are consistent with a main role played by β receptors in the relaxation of circular smooth muscle and with a selective involvement of α2 receptors in peristalsis inhibition. The pattern of sensitivity changes is consistent with a high degree of physiological modulation by sympathetic supply both on the smooth muscle and on the intramural nervous structures. Both pre- and postjunctional mechanisms could be responsible for the development of supersensitivity, but the former seem to operate only at interneuronal synapses. The opposite sensitivity changes observed for noradrenaline and clonidine suggest a different effect of two agonists at the presynaptic level.

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, Section of Pharmacology, University of Pavia, Piazza Botta 10, I-27100, Pavia, Italy

    G. M. Frigo, S. Lecchini, M. Marcoli, M. Tonini, L. D'Angelo & A. Crema

Authors
  1. G. M. Frigo
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  2. S. Lecchini
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  3. M. Marcoli
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  4. M. Tonini
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  5. L. D'Angelo
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  6. A. Crema
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Frigo, G.M., Lecchini, S., Marcoli, M. et al. Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation. Naunyn-Schmiedeberg's Arch. Pharmacol. 325, 145–152 (1984). https://doi.org/10.1007/BF00506194

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  • DOI: https://doi.org/10.1007/BF00506194

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