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Effects of neuronal polypeptides on intestinal smooth muscle; a comparison with non-adrenergic, non-cholinergic nerve stimulation and ATP

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Abstract

Substance P, somatostatin, enkephalin and vasoactive intestinal polypeptide (VIP) did not mimic the inhibitory responses to non-adrenergic, non-cholinergic nerve stimulation. Substance P (0.1–10 μg/ml) always caused contraction, enkephalin (0.1–10 μg/ml) and somatostatin (0.1–10 μg/ml) were inactive, while VIP (0.01–1 μ/ml) produced very slow relaxation, taking about 4 min to reach a maximum after a latency of about 60 sec. Low concentrations of neurotensin (1–10 ng/mg) caused contraction, but a higher concentrations (50–1000 ng/ml) it produced a biphasic response which consisted of an initial contraction followed by a slow relaxation. In high tone preparations, the slow relaxation did not mimic the nerve-mediated response, taking approximately 43 sec. to reach maximum, after a long latency of about 15 sec. In contrast, ATP (0.1–50 μg/ml) mimicked closely the rapid responses to non-adrenergic, non-cholinergic nerve stimulation in all preparations, whether the tone was low, medium or high. The time for the inhibitory response to reach maximum was about 15 sec after a latency of approximately 1 sec. Indomethacin (3.4–34 μg/ml) did not unmask any inhibitory responses to any of the peptides. It is concluded that ATP remains the most likely substance to be the inhibitory transmitter released from non-adrenergic, non-cholinergic nerves supplying the smooth muscle of the taenia coli.

References (57)

  • J.M. Polak et al.

    Enkephalin-like immuno-reactivity in the human gastrointestinal tract

    Lancet

    (1977)
  • M.R. Bennett

    Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves

    J. Physiol. (London)

    (1966)
  • S.R. Bloom et al.

    Peptidergic versus purinergic

    The Lancet

    (1978)
  • E. Bulbring

    Measurements of oxygen consumption in smooth muscle

    J. Physiol. (London)

    (1953)
  • G. Burnstock

    Evolution of the autonomic innervation of visceral and cardio-vascular systems in vertebrates

    Pharmacol. Rev.

    (1969)
  • G. Burnstock

    Purinergic nerves

    Pharmacol. Rev.

    (1972)
  • G. Burnstock

    Purinergic transmission

  • G. Burnstock

    Past and current evidence for the purinergic nerve hypothesis

  • G. Burnstock et al.

    Inhibition of the smooth muscle of the taenia coli

    Nature

    (1963)
  • G. Burnstock et al.

    The inhibitory innervation of the taenia of the guinea pig caccum

    J. Physiol. (London)

    (1966)
  • G. Burnstock et al.

    Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut

    Brit. J. Pharmacol. Chemotherap.

    (1970)
  • G. Burnstock et al.

    Evidence for purinergic innervation of the anococygeus muscle

    Brit. J. Pharmacol.

    (1978)
  • R.W. Bury et al.

    A pharmacological investigation of synthetic substance P on the isolated guinea-pig ileum

    Clin. Exptl. Pharmacol. Physiol.

    (1977)
  • G. Campbell

    Nerve-mediated excitation of the taenia of the guinea-pig caecum

    J. Physiol. (London)

    (1966)
  • G. Campbell

    Autonomic nervous supply to effector tissues

  • R.D. Cook et al.

    The ultrastructure of Auerbach's plexus in the guinea-pig. 1. Neural elements

    J. Neurocytol.

    (1976)
  • R. Dingledine et al.

    Effects of synaptic transmission blockade on morphine action in the guinea-pig myenteric plexus

    J. Pharmacol. Exptl. Therap.

    (1976)
  • R. Franco et al.

    The Effect of substance P on intestinal nerves and muscle

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