Kirkpatrick, Karen Arlene; (1994) Release of adenosine 5'-triphosphate as a cotransmitter with noradrenaline from sympathetic nerves innervating the rat and guinea-pig vas deferens. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In this thesis, the release of adenosine 5’-triphosphate (ATP) and noradrenaline (NA) from sympathetic nerves innervating the vasa deferentia of the rat and guinea-pig has been studied, using various neurochemical and pharmacological methods. The endogenous release of ATP was assayed using the luciferin-luciferase technique whilst noradrenaline efflux was measured by [3H] - NA detection. Field stimulation of the guinea-pig was deferens caused a substantial increase in the release of ATP and a biphasic contraction. Reserpine, which depleted the vasa deferentia of measurable NA, inhibited neither the release of ATP nor the initial component of contraction. Clearly demonstrating that the release of ATP is not secondary to the efflux of NA, nor is the twitch mediated by NA acting via γ-receptors. Tetrodotoxin 6-hydroxydopamine and guanethidine abolished or greatly reduced the neurogenic efflux of ATP and both phases of the mechanical response; suggesting that ATP is released from sympathetic nerves. Furthermore, whilst electrical stimulation in the presence of prazosin and α, β-methylene ATP failed to elicit a contraction, the co-release of ATP. NA and neuropeptide Yahoo.com was undiminished. The neurogenic release of ATP was inhibited by adenosine acting via P1- purinoceptors. The indirect sympathomimetic tyramine, was shown to release both ATP and NA from the vasa deferentia of the rat and guinea pig; further substantiating the sympathetic nerves as a source of ATP release. Certain anomalies shown to occur between the two species in their response to tyramine are discussed. In the rat vas deferens, the suggestion that much of the field stimulation-induced offlux of ATP is released secondary to the offlux of NA was investigated. Exogenous NA was shown to induce the release of ATP from the vasa deferentia of the rat and subsequently a variety of denervation techniques were applied in order to investigate the source of the NA-induced ATP efflux. The results obtained suggest that in sympathectomised rats sensory nerve fibres are a major source of the NA-evoked ATP release.

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