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Activation of the micturition reflex by NK 2 receptor stimulation in the anaesthetized guinea‐pig
Author(s) -
Bushfield Mark,
Metcalfe Maria,
Naylor Alasdair M.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15891.x
Subject(s) - hexamethonium , atropine , endocrinology , ppads , purinergic receptor , muscarinic acetylcholine receptor , agonist , chemistry , medicine , stimulation , chlorisondamine , guanethidine , reflex , pharmacology , receptor , biology , blood pressure
1 The mechanisms underlying stimulation of bladder contractions and bronchoconstriction by the selective NK 2 receptor agonist, [β‐Ala 8 ]NKA(4–10), were examined in the anaesthetized guinea‐pig. 2 Atropine, α,β‐methylene‐ATP and ganglion blocking agents were used to examine the contribution of reflex arc activation and/or potentiation of efferent mechanisms to the NK 2 receptor‐mediated responses seen in these two tissues. 3 [β‐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 P 2 purinoceptors by α,β‐methylene‐ATP. 4 At doses of 5 μg kg −1 and above, [β‐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 α,β‐methylene‐ATP, resulted in partial inhibition of bladder contractile responses to [β‐Ala 8 ]NKA(4–10). The combination of atropine and α,β‐methylene‐ATP pretreatment resulted in additive inhibition leading to complete blockade of the response. 6 The bladder responses to [β‐Ala 8 ]NKA(4–10) (5 μg 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 NK 2 receptors in the anaesthetized guinea‐pig. Contractions occur secondary to the release of endogenous cholinergic and NANC transmitters by activation of neuronal NK 2 receptors located at a preganglionic site, possibly on capsaicin‐sensitive sensory afferent nerves, where NK 2 sites have been demonstrated autoradiographically. In contrast, [β‐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.