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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 335 (1987), S. 629-635 
    ISSN: 1432-1912
    Keywords: GABAA agonists ; Substance P ; Cholinergic neurons ; Guinea-pig ileum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 324 (1983), S. 180-184 
    ISSN: 1432-1912
    Keywords: GABA ; 5-Hydroxytryptamine ; Guinea-pig ileum ; Desensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. GABA (3–100 μM) and 5-HT (0.03–30 μM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. 2. The contractile response to GABA was antagonized by hyoscine (2.2 μM), TTX (0.7 μM), bicuculline (3 μM), furosemide (25 μM) and desensitization to GABA itself, while hexamethonium (20 μM) and methysergide (20 μM) were without effect. 3. The contractile response to 5-HT was antagonized by hyoscine (2.2 μM), TTX (0.7 μM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 μM), hexamethonium (20 μM), furosemide (25 μM) and methysergide (20 μM). 4. A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 μM) concentrations of GABA. 5. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.
    Type of Medium: Electronic Resource
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