Effects of Desensitization to Adenosine 5′‐triphosphate and Adenosine on Non‐adrenergic Inhibitory Responses in the Circular Muscle of Rabbit Colon

Abstract

1 An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 pM) of these compounds.2 The desensitization was specific and reversible after prolonged washing. It could be overcome by increasing the concentrations of the purine agonists. 3 Dipyridamole potentiated the non-adrenergic inhibition in response to transmural stimulation but failed to influence the caudad relaxation evoked by radial distension. 4 Desensitization to ATP and adenosine (and to ATP + adenosine simultaneously) did not affect the non-adrenergic inhibition in response to radial distension or transmural stimulation. 5 These results suggest that neither ATP nor adenosine are the final transmitters mediating the non-adrenergic inhibitory responses in the distal colon of the rabbit.

Purine receptors in the guinea‐pig internal anal sphincter

“…Even though the antagonism appeared to be non-competitive (at variance with the results obtained by Choo (1980) in guinea-pig detrusor), and non-specific at higher concentrations, our findings suggest the presence of two separate purinoceptors on the smooth muscle cells of the guinea-pig internal anal sphincter. Desensitization to the muscular action of purine compounds has been used as a mean of assessing the purinergic nerve hypothesis both in the longitudinal (Tonini, Onori, Frigo, Lecchini, d'Angelo & Crema, 1981) and circular muscle of rabbit colon (Crema, d'Angelo, Frigo, Lecchini, Onori & Tonini, 1982). The present preparation did not show tachyphylaxis after repeated exposure to purine compounds, thus the nerve-mediated relaxation was studied in the presence of reactive blue 2 and after saturation of the purinoceptors by either ATP or adenosine.…”

In memoriam of a master of neurogastroenterology: Marcello Tonini (1944–2010)

“…Once back in Pavia, Marcello produced many insightful results regarding neurogenic control of intestinal muscle contraction with special emphasis on peristalsis. Using elegant pharmacological approaches, he made significant contributions to the current knowledge on the complex neural mechanisms controlling gut motor function by establishing roles for purinergic, cholinergic, GABAergic and serotonergic pathways 2–4 . During this stage of his career, Marcello visited, in different occasions, the Department of Human Physiology and Centre for Neuroscience at the Flinders University in South Australia directed by Marcello Costa with whom he established a lifelong scientific collaboration and fraternal friendship.…”