1. The possibility that a purine nucleotide is involved in excitatory transmission to the urinary bladder has been tested. All the purine compounds tested which contained a pyrophosphate bond produced contraction, adenosine triphosphate (ATP) being the most potent. Adenosine and adenosine monophosphate caused relaxation.

2. The response to ATP closely mimicked the nerve-mediated contraction, both being characterized by a rapid contraction which was not maintained. A lack of sensitivity to ATP was noted in some preparations of the rat urinary bladder.

3. Both nerve-mediated contractions and contractions caused by ATP were blocked by quinidine, while the response to acetylcholine persisted.

4. Nerve-mediated responses were depressed during tachyphylaxis produced by high concentrations of ATP. Tachyphylaxis did not occur when low concentrations were used. Possible explanations for these results are discussed.

5. The results are consistent with the hypothesis that non-cholinergic excitatory nerves to the guinea-pig bladder release a purine nucleotide, but do not provide critical evidence for it.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1972.tb07283.x

Atropine resistant excitation of the urinary bladder: The possibility of transmission via nerves releasing a purine nucleotide

Mechanism of transmitter release.

1. The responses to non-adrenergic, non-cholinergic nerve stimulation have been compared with those to exogenously applied ATP on seventeen different tissues from a number of vertebrate classes.2. Stimulation of all the mammalian gut preparations studied (with the exception of the guinea-pig ileum) after blockade of the effects of adrenergic and cholinergic nerve stimulation by guanethidine (3.5 muM) and hyoscine (1.3 muM) caused inhibition; exogenously applied ATP mimicked this inhibitory response.3. Stimulation of the guinea-pig ileum in the presence of hyoscine and guanethidine, usually caused a diphasic response, relaxation followed by contraction; exogenously applied ATP mimicked this response, in contrast to acetylcholine and noradrenaline which caused excitation and relaxation respectively.4. Stimulation of preparations of lower vertebrate gut and guinea-pig bladder in the presence of hyoscine and guanethidine caused contraction; exogenously applied ATP mimicked this contractile response.5. In each preparation the time course of the response to ATP was similar or identical to the response to non-adrenergic, non-cholinergic nerve stimulation.6. The results are consistent with the hypothesis that a purine nucleotide may be the transmitter substance released from non-adrenergic, non-cholinergic nerves supplying smooth muscle preparations from a number of vertebrate classes.

A comparison of the excitatory and inhibitory effects of non‐adrenergic, non‐cholinergic nerve stimulation and exogenously applied ATP on a variety of smooth muscle preparations from different vertebrate species

The majority of studies of the functional distribution of purinoceptors have been carried out with mammalian preparations. The objective of this article is to review the disparate literature describing purinoceptor-mediated effects in invertebrates and lower vertebrates and, in view of the concept that ontogeny repeats phylogeny, to review also the evidence for purinoceptor involvement in the complex signaling involved in embryonic development. Even with the limited information currently available, it is clear that purinoceptors are involved in early signalling in vertebrate embryos; one novel G protein-coupled P2Y receptor has already been cloned and characterized in frog embryo and hopefully more will follow. It is also clear that purinoceptors for both adenosine and ATP are present in early evolution and play a number of different roles in most, if not all, invertebrate and lower species. However, until selective agonists and antagonists are identified for the recently cloned purinoceptors subtypes in vertebrates, it will not be possible to resolve questions concerned with the evolution of these subtypes. Molecular cloning of genes encoding receptors for purines and pyrimidines from invertebrates and lower vertebrates represents an alternative approach to advancing knowledge in the area.

Purinoceptors: Ontogeny and phylogeny

Studies on the vascular smooth muscle responses to histamine and 5-hydroxytryptamine and on the distribution of these amines in different tissues were performed in several species of reptiles. The responses to adrenaline, noradrenaline and acetylcholine were studied for comparison. Vascular actions were recorded both in vivo as changes in systemic arterial blood pressure and in vitro as changes in vascular resistance in perfused preparations. The specificity of the action of each drug was evaluated by means of pharmacological blocking agents. Tissue levels of histamine and 5-hydroxytryptamine were determined spectrofluorometrically. Fluorescence microscopy was used for histochemical localization of the histamine stores. The results indicate that histamine and 5-hydroxytryptamine exert dual actions (inhibitory and stimulatory) on reptilian vascular smooth muscles which have thus acquired response patterns towards these amines similar to those found in mammals. Inhibitory as well as stimulatory actions of adrena line, noradrenaline and acetylcholine are also present in reptiles. Levels of 5-hydroxytrypt amine are apparently low in most tissues, whereas many species show very high tissue levels of histamine. Histamine, except that of the stomach, is mainly located in tissue mast cells and blood basophils. Nutritional-dependent variations in mast cell number are parallelled by varia tions in tissue histamine content. By comparing the present results with those previously ob tained in jawless vertebrates, fish and amphibians, a general outline of the evolution of vascular actions and tissue stores of histamine and 5-hydroxytryptamine is presented.

M.J. Wood

Papers

Innervation of the lungs of the sleepy lizard (Trachysaurus rugosus)—II. physiology and pharmacology

Innervation of the lungs of the toad (Bufo marinus)—I. Physiology and pharmacology

Innervation of the urinary bladder of the sleepy lizard (Tracysaurus rugosus)—II. Physiology and pharmacology