Effects of tachykinins on myenteric neurones of the guinea-pig gastric corpus: involvement of NK-3 receptors

Responses of gastric myenteric neurones evoked by the mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were investigated using conventional intracellular recording methods. Application of the tachykinins caused a long lasting depolarization of the membrane potential which was associated with increased spike discharge and augmented excitability of the cells. The responses slowly desensitized. Additionally, cross desensitization occurred between SP, NKA and NKB. Both the NK-1 receptor agonist [Sar⁹,MetO₂¹¹]SP and the NK-2 receptor agonist [β-Ala⁸]NKA_(4-10) had no effect on the electrical properties of the neurones. Only the NK-3 receptor agonist [MePhe⁷]NKB mimicked the excitatory response observed during SP, NKA and NKB applications. [MePhe⁷]NKB-induced desensitization abolished the response to SP, NKA and NKB. However, long lasting applications of [Sar⁹,MetO₂¹¹]SP or [β-Ala⁸]NKA_(4-10) had no effect on the SP, NKA or NKB responses. The excitatory effect of SP, NKA and NKB remained unchanged during application of the tachykinin analogues [D-Arg¹, d-Trp^7,9,Leu¹¹]SP and [Tyr⁵, d-Trp^6,8,9,Arg¹⁰]NKA_(4-10). The results indicate that SP, NKA and NKB act as excitatory neuromodulators within the enteric nervous system of the stomach. The effects of SP, NKA and NKB appeared to be mediated by activation of NK-3 receptors.