| Summary: | <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The basic mechanisms regulating the function of the bladder and urethra, under both normal and abnormal conditions, are still incompletely understood, and consequently, many treatments are both empirical and unsatisfactory.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">This thesis examines the physiology and pharmacology of lower urinary tract smooth muscles from rabbit, pig and cat, utilising isometric tension recording of strips of muscle taken from the lower urinary tract of these three species. Abundant cholinergic innervation of the bladder in all three species was demonstrated. Alpha-adrenoceptors predominated in the urethra, whereas responses to beta-adrenoceptors predominated in the bladder body, though alpha-adrenoceptors were present in the posterior detrusor of the rabbit.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The present studies confirmed that non-adrenergic, non-cholinergic transmitters are involved in the mechanism regulating function of the lower urinary tract. Contractile responses were seen in response to application of ATP and 5-HT. The 5-HT response was diminished by atropine and α,β-methylene ATP. A combination of these drugs diminished the contractile response more than either alone. Evidence is presented for the presynaptic action of 5-HT, causing release of acetylcholine and a non-adrenergic, non-cholinergic transmitter in the rabbit lower urinary tract, probably mediated via the 5-HT<sub>3</sub> receptor, identified by the use of several putative 5-HT antagonists.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">This thesis suggests that high KCl-induced contraction is due to initiation of depolarization of the smooth muscles membrane, triggering the opening of Ca channels, Ca entry and subsequent contraction. High KCl-induced relaxation in the pig urethra is unlikely to occur by stimulation of inhibitory nerves or by activation of the Na pump.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The results of the histological studies agree with the pharmacological study in the conclusion that the autonomic innervation of the lower urinary tract of small mammals contains non-adrenergic, non-cholinergic innervation in addition to sympathetic and parasympathetic nerves.</p> <p xmlns:etd="http://www.ouls.ox.ac.uk/ora/modsextensions">The development of specific agonists and antagonists to the receptors mediating the responses may play an important role in the future treatment of abnormal micturition.</p>
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