Further evidence for involvement of adenosine-5′-triphosphate in non-adrenergic non-cholinergic relaxation of the isolated rat duodenum

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Abstract

The nature of the inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter responsible for neurogenic relaxation of rat duodenum was studied with in vitro techniques. Adenosine 5′-triphosphate (ATP)(1 mM), γ-aminobutyric acid (GABA, 1 mM), dimethylphenylpiperazinium (DMPP, 0.1 mM) and field stimulation (60 V, 2 ms, 0.1 Hz) produced transient relaxation followed by rebound contraction. In contrast vasoactive intestinal polypeptide (VIP) (0.3 μM) and noradrenaline (1 μM) induced relaxation which set in more slowly and lasted longer. Tetrodotoxin (0.85 μM) abolished field stimulation-induced relaxation but not ATP-, VIP- or noradrenaline-induced relaxation. Nucleotide pyrophosphatase (0.25 U/ml), but not the proteolytic enzyme α-chymotrypsin (2 U/ml), selectively antagonized NANC relaxation. The rank order of potency of various adenine derivatives for inducing relaxation was adenosine-5′-triphosphate > adenosine-5′-diphosphate ⪢ adenosine > adenosine-5′-monophosphate. ATP-induced relaxation was selectively antagonized by the putative P2 purinoceptor antagonist reactive blue 2, but unaffected by the selective P1 purinoceptor antagonist 8-phenyltheophylline. The duration of ATP- as well as β-γ-methylene adenosine-5′-triphosphate (a stable analogue of ATP)-induced relaxation was similar and was unaffected by indomethacin 10 μM (which abolished the rebound contraction). In those preparations whose contractile tone was increased by using a high-K+ medium the ability of ATP to elicit relaxation was markedly reduced, while GABA- and DMPP-induced relaxation was abolished. On the other hand, ATP-, GABA- and DMPP-induced relaxation of the tonic component of 5-hydroxytryptamine (5-HT)(0.1 mM)-induced contraction was similar to that observed in control conditions. These findings add further weight to the proposal that endogenous ATP is involved in determining NANC relaxation of rat duodenum.

References (38)

  • P. Sneddon et al.

    ATP as a cotransmitter in rat tail artery

    European J. Pharmacol.

    (1984)
  • D.P. Westfall et al.

    The postjunctional effects and neural release of purine compounds in guinea-pig was deferens

    European J. Pharmacol.

    (1978)
  • F. Angel et al.

    Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa

    J. Physiol. (London)

    (1983)
  • N. Anwar et al.

    Two actions of γ-aminobutyric acid on the responses of the isolated basilar artery from the rabbit

    Br. J. Pharmacol.

    (1982)
  • B.E.C. Banks et al.

    Apamin blocks certain neurotransmitter induced increases in potassium permeability

    Nature

    (1979)
  • V. Bartlett et al.

    Evidence for two adenine derivative receptors in rat ileum which are not involved in the nonadrenergic, noncholinergic response

    Can. J. Physiol. Pharmacol.

    (1979)
  • V. Bauer et al.

    TEA-sensitive potassium conductance changes induced by 1-adrenoceptor and ATP-receptor activation in guinea-pig taenia coli

    Gen. Physiol. Biophys.

    (1982)
  • C. Brown et al.

    Effects of ATP and β-γ methylene ATP on rat urinary bladder

    Br. J. Pharmacol.

    (1979)
  • G. Burnstock

    Neurotransmitters and trophic factors in the autonomic nervous system

    J. Physiol. (London)

    (1981)
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      ATP (via adenosine) also inhibited release of acetylcholine (ACh) from enteric neurons (Hayashi et al., 1978; Sawynok and Jhamandas, 1976; Wiklund et al., 1985). Evidence was presented to satisfy the view that responses of the small intestine to transmural nerve stimulation were mediated, at least, in part, by ATP in guinea pig ileum (Crist et al., 1992; He and Goyal, 1993; Ohkawa, 1974) and rat duodenum (Manzini et al., 1985, 1986a). ATP and ADP produced inhibitory effects on peristalsis (Okwuasaba and Hamilton, 1975).

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