Date of Award
1989
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
Although the role of adenosine in the inhibition of acetylcholine release from myenteric neurons of the small intestine is firmly established, the classification and characteristics of such receptors have not been adequately described. Unlike in the central nervous system, it is not clear if heterogeneity of adenosine receptors exists, or if nucleoside-mediated inhibition of the release of other neuromediators occurs in the enteric nervous system. The studies reported in this thesis were directed at these questions.;Adenosine recognition sites were characterized in ligand binding studies at purified myenteric varicosities. The receptor nature of the binding sites labelled by selective adenosine analogs is supported by the saturability of binding, the good correlation between binding affinity and biological activity (ie. inhibition of Ach release) as well as the potency of adenosine receptor antagonists in displacing their specific binding.;Evidence was obtained for the presence of a heterogeneous population of adenosine receptors on enteric nerve endings. The data is consistent with the presence of A{dollar}\sb1{dollar}-like adenosine receptors with affinity for both N{dollar}\sp6{dollar}- and 5{dollar}\sp\prime{dollar}- substituted adenosine analogs, as well as A{dollar}\sb2{dollar} adenosine receptors with affinity only for 5{dollar}\sp\prime{dollar}-N-ethylcarboxamide adenosine. The A{dollar}\sb2{dollar} receptor may be present in higher concentrations on enteric nerve endings.;Adenosine mediated inhibition of tachykinin release was demonstrated using cholecystokinin (CCK-8) and field-stimulated responses of atropinized guinea pig ileal strips. The data obtained indicates that the same adenosine receptor inhibits the release of both acetylcholine and tachykinins.;The presence of substantial quantities of alpha-neurokinin, substance P, met-enkephalin, leu-enkephalin and gastrin releasing polypeptide (GRP) in this synaptosomal preparation suggested its possible utility in functional studies on modulation of release of endogenous peptides by nucleosides. The finding of both potassium evoked- and GRP mediated-release of several neuropeptides from crude synaptosomal suspensions support this contention.
Recommended Citation
Christofi, Fedias Leontiou, "Studies On Adenosine-mediated Neuromodulation In The Enteric Nervous System" (1989). Digitized Theses. 1778.
https://ir.lib.uwo.ca/digitizedtheses/1778