Inhibitory Effect of Purinergic Antagonists to the Electrically Stimulated Contraction of Canine Detrusor Muscle

Cho, Seung Phil; Hong, Jun Hyuk; Kim, Choung Soo; Ahn, Tai Young

Abstract

Cholinergic neurotransmission plays a major role in the postganglionic nerve evoked contractile response of the urinary bladder, but there is atropine-resistant contraction that is not completely blocked by atropine and may be related with nonadrenergic-noncholinergic (NANC) neurotransmission. Among the NANC neurotransmission, adenosine triphosphate(ATP) is an important transmitter in purinergic neurotransmission which is known to many vertebrates including human beings. The aim of this study is to determine the role and existence of purinergic neurotransmission in the canine detrusor muscle. In vitro contractile responses to electrical stimulation after pretreatment with atropine were measured in the presence of purinergic antagonist such as theophylline, b, r-methylene ATP and verapamil. Field stimulation( frequency 0.5-40 Hz; pulse width l ms; 10V square wave) produced a contraction that was abolished by tetrodotoxin( 0.1uM) and reduced by 42.5% after atropine ( 10uM) pretreatment. The contractile response was reduced by 44.1%, 30.3% and 60.1 % after the treatment of theophylline( 1uM, 10uM and 100uM) in the presence of atropine, 11.1%, 22.7% and 30.3% after the treatment of b, r-methylene ATP ( 5uM, 50uM and 500uM) and 17.6%, 39.4% and 60.1 % after the treatment of verapamil( 0.1u M, 1uM and 10uM) at 20 Hz frequency. These reduced contractile responses were statistically significant (p <0.05), especially in higher concentration, and relatively frequency-dependent and verapamil decreased the contractile response most significantly. These data demonstrate that purinergic neurotransmission is related to the contraction of canine detrusor muscle. On the other hand contractile responses were persisted after pretreatment of higher dose antagonist, which suggests that another mechanism such as peptidergic mechanism be related to the contraction of canine detrusor muscle.