Contribution of adrenergic and "purinergic" neurotransmission to contraction in rabbit detrusor

Abstract

In the presence of propranolol, norepinephrine produced an alpha adrenoceptor mediated contraction in isolated rabbit detrusor. Phenoxybenzamine (3.3 x 10(-8) M) antagonized this response but failed to affect the contraction produced by field stimulation either in normal or in hemicholinium-3-treated tissue. Higher concentrations of phenoxybenzamine were antagonistic to carbachol. Electrically induced contractions were also unaffected by guanethidine (1 x 10(-4) M) in vitro. Reserpine pretreatment produced no change in the contractile response although the tissue was depleted of catecholamine fluorescence on histology. It is concluded that adrenergic neurotransmission does not account for noncholinergic excitatory neurotransmission in rabbit detrusor. In rabbit detrusor adenosine 5'-triphosphate (ATP) produced a transient contraction which was not antagonized by tetrodotoxin (1 x 10(-7) M), atropine (4 x 10(-7) M) or phenoxybenzamine (3.3 x 10(-7) M). Adenosine, adenine phosphate and adenosine 5'-monophosphate had little or no effect, while sodium tripolyphosphate and adenosine 5'-diphosphate produced a smaller response than ATP. Dipyridamole (1 x 10(-8)-1 x 10(-5) M) did not unmask a response to adenosine and did not potentiate the response to ATP or field stimulation. Theophylline (5 x 10(-5) M) and 2, 2'-pyridylisatogen (PIT) (1 X 10(-5) M) depressed responses to ATP without antagonizing those to carbachol. At these doses, theophylline and 2, 2'-pyridylisatogen also antagonized the electrically induced contraction. Desensitization with ATP (1.5 X 10(-3) M for 30 min) selectively depressed responses to ATP but not to carbachol, and also depressed the response to field stimulation, particularly at frequencies of 10 Hz and lower. It is at these frequences that the noncholinergic component of the contractile response is most significant. Combination of the desensitization procedure with atropine produced an additive effect, suggesting that the two mechanisms affected are independent. Combination of the desensitization procedure with hemicholinium-3 produced less than an additive effect, suggesting an interference between the two treatments. It is concluded that ATP plays a role in the noncholinergic component of excitatory neurotransmission in rabbit detrusor.