Involvement of substance P in the excitatory action of GABAA agonists on cholinergic neurons in the guinea-pig ileum

M. Tonini, L. Onori, C. A. Rizzi, E. Perucca, L. Manzo, A. Crema

Research output: Contribution to journalArticle

Abstract

1. The possible involvement of substance P (SP) in cholinergic contractions induced by GABAA agonists in the guinea-pig ileum was further investigated. 2. Responses evoked by 3-aminopropane sulphonic acid (3-APS) or muscimol consisted of a rapid phasic contraction followed in 70% of preparations by a tonic contraction, usually smaller in amplitude but considerably longer in duration. Phasic and tonic components were sensitive to bicuculline, neurogenic (cholinergic) in nature and susceptible to desensitization. 3. Capsaicin (0.2 μM) pretreatment and SP receptor desensitization caused by 3 different priming SP concentrations (10 nM, 30 nM, 100 nM), depressed both components of the 3-APS-induced response, the magnitude of antagonism being greater for tonic contractions. Similar findings were obtained by using 10 μM (d-Pro4, d-Trp7,9)SP-(4–11), even though the degree of antagonism caused by this SP antagonist was consistently lower. 4. These results indicate that depression of SP receptor function achieved by three different procedures decreases cholinergic contractile responses to GABAA agonists in the guinea-pig ileum. This provides further support for the hypothesis that GABAA receptor activation evokes both direct and indirect stimulation of enteric cholinergic neurons and that SP and/or a related peptide play an important role in mediating the indirect component of the cholinergic response.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume335
Issue number6
DOIs
Publication statusPublished - 1987

Keywords

  • Cholinergic neurons
  • GABA agonists
  • Guinea-pig ileum
  • Substance P

ASJC Scopus subject areas

  • Pharmacology

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