ACTIVATION OF THE MICTURITION REFLEX BY NK2 RECEPTOR STIMULATION IN THE ANESTHETIZED GUINEA-PIG

1 The mechanisms underlying stimulation of bladder contractions and bronchoconstriction by the selective NK2 receptor agonist, [beta-Ala(8)]NKA(4-10), were examined in the anaesthetized guinea-pig. 2 Atropine, alpha,beta-methylene-ATP and ganglion blocking agents were used to examine the contribution of reflex are activation and/or potentiation of efferent mechanisms to the NK2 receptor-mediated responses seen in these two tissues. 3 [beta-Ala(8)]NKA(4-10)-induced bronchoconstriction was immediate, dose-dependent and was unaffected by pretreatment with ganglion blockers (hexamethonium or chlorisondamine), blockade of muscarinic receptors by atropine, or desensitization of beta(2) purinoceptors by alpha,beta-methylene-ATP. 4 At doses of 5 mu g kg(-1) and above, [beta-Ala(8)]NKA(4-10) induced bladder contractions that appeared to be of an 'all-or-nothing' nature. These contractions occurred after a delay of 10 to 30 s and were often biphasic, comprised of an initial rapid component followed by a slower tonic component. 5 Pretreatment of the animals with either atropine or the desensitizing purinoceptor agonist alpha,beta-methylene-ATP, resulted in partial inhibition of bladder contractile responses to [beta-Ala(8)]NKA(4-10). The combination of atropine and alpha,beta-methylene-ATP pretreatment resulted in additive inhibition leading to complete blockade of the response. 6 The bladder responses to [beta-Ala(8)]NKA(4-10) (5 mu g kg(-1)) were inhibited by pretreatment with the ganglion blockers, hexamethonium and chlorisondamine, indicating a preganglionic mechanism of action. 7 These findings demonstrate the indirect nature of the bladder contractions induced by activation of NK2 receptors in the anaesthetized guinea-pig. Contractions occur secondary to the release of endogenous cholinergic and NANC transmitters by activation of neuronal NK2 receptors located at a preganglionic site, possibly on capsaicin-sensitive sensory afferent nerves, where NK2 sites have been demonstrated autoradiographically. In contrast, [beta-Ala(8)]NKA(4-10)-induced bronchoconstriction in the anaesthetized guinea-pig is a direct smooth muscle contractile response that is unaffected by ganglion blockade or blockade of muscarinic receptors.