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Title: Characterisation of the responses, and possible mechanisms behind, spontaneous phasic activity in the isolated guinea pig bladder
Author: Finney, Steven M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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The intrinsic characteristics of spontaneous, phasic activity in response to volume have revealed a period of inhibition following volume reduction termed the inhibitory phase. This is dependent upon the magnitude and duration of volume increase prior to decrease and is regulated by a distinct mechanism comprising of a combination of excitatory and inhibitory stimuli that may be co-ordinated by ganglia. It has also been found to be manipulated by antimuscarinics, nicotinic antagonists and purinergic agonists suggesting its underlying generation and regulation to be complex. The actions of hexamethonium and pancuronium upon phasic activity have suggested the presence of non-ganglionic nicotinic receptors involved in the modulation of spontaneous and volume induced activity; in addition to the role of ganglionic nicotinic receptors in co-ordinating the return of activity during the inhibitory phase. Purinoceptors were found to display a varied and complex response, both on pacemaker activity and upon the inhibitory phase. Both excitatory and inhibitory receptors were present; however, individual subtypes seemed to display a differing degree of functional relevance, varying between low and high volume. Though P2X and P2Y may have excitatory and inhibitory effects respectively, the overall effect of purinergic receptor stimulation upon phasic activity seems to be inhibitory. These experiments illustrate the mechanisms involved in the generation and co-ordination of spontaneous activity to be complex. It highlights novel mechanisms through which acetylcholine and adenosine triphosphate may be exerting an effect, and may account for the therapeutic actions of antimuscarinic medications. It also highlights potential mechanisms which may act as further therapeutic targets in the development of newer drugs for the treatment of OAB.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available