Activation of the micturition reflex by NK2 receptor stimulation in the anaesthetized guinea-pig.

Abstract

1. The mechanisms underlying stimulation of bladder contractions and bronchoconstriction by the selective NK2 receptor agonist, [beta-Ala8]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 arc activation and/or potentiation of efferent mechanisms to the NK2 receptor-mediated responses seen in these two tissues. 3. [beta-Ala8]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 P2 purinoceptors by alpha,beta-methylene-ATP. 4. At does of 5 micrograms kg-1 and above, [beta-Ala8]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-Ala8]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-Ala8]NKA(4-10) (5 micrograms 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 apreganglionic site, possibly on capsaicin-sensitive sensory afferent nerves, where NK2 sites have been demonstrated autoradiographically. In contrast, [beta-Ala8]NKA(4- 10)-induced bronchoconstriction in the anaesthetized guinea-pig is a direct smooth muscle contractile response that is unaffected by ganglionblockade or blockade of muscarinic receptors.

• Authors: M Bushfield, M Metcalfe, A M Naylor
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 115 Issue 6 Pg. 875-82 (Jul 1995) ISSN: 0007-1188 [Print] England
• PMID: 7582514 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Ganglionic Blockers
• Piperidines
• Receptors, Neurokinin-2
• SR 48968
• Atropine

Topics

• Animals
• Atropine (pharmacology)
• Benzamides (pharmacology)
• Bronchi (drug effects)
• Dose-Response Relationship, Drug
• Female
• Ganglionic Blockers (pharmacology)
• Guinea Pigs
• Piperidines (pharmacology)
• Receptors, Neurokinin-2 (agonists, drug effects)
• Reflex (drug effects)
• Urinary Bladder (drug effects)
• Urination (drug effects)