Article date: July 1995
By: Mark Bushfield, Maria Metcalfe, Alasdair M. Naylor, in Volume 115, Issue 6, pages 875-882
The mechanisms underlying stimulation of bladder contractions and bronchoconstriction by the selective NK2 receptor agonist, [β‐Ala8]NKA(4–10), were examined in the anaesthetized guinea‐pig.
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 NK2 receptor‐mediated responses seen in these two tissues.
[β‐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 α,β‐methylene‐ATP.
At doses of 5 μg kg−1 and above, [β‐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.
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‐Ala8]NKA(4–10). The combination of atropine and α,β‐methylene‐ATP pretreatment resulted in additive inhibition leading to complete blockade of the response.
The bladder responses to [β‐Ala8]NKA(4–10) (5 μg kg−1) were inhibited by pretreatment with the ganglion blockers, hexamethonium and chlorisondamine, indicating a preganglionic mechanism of action.
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, [β‐Ala8]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.
The mechanisms underlying stimulation of bladder contractions and bronchoconstriction by the selective NK2 receptor agonist, [β‐Ala8]NKA(4–10), were examined in the anaesthetized guinea‐pig.
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 NK2 receptor‐mediated responses seen in these two tissues.
[β‐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 α,β‐methylene‐ATP.
At doses of 5 μg kg−1 and above, [β‐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.
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‐Ala8]NKA(4–10). The combination of atropine and α,β‐methylene‐ATP pretreatment resulted in additive inhibition leading to complete blockade of the response.
The bladder responses to [β‐Ala8]NKA(4–10) (5 μg kg−1) were inhibited by pretreatment with the ganglion blockers, hexamethonium and chlorisondamine, indicating a preganglionic mechanism of action.
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, [β‐Ala8]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.
DOI: 10.1111/j.1476-5381.1995.tb15891.x
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