Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Alfaxalone (1-100 nM) potentiated gamma-aminobutyric acidA (GABAA)-receptor-mediated contractile responses in the guinea-pig isolated ileum, with a leftward shift of the GABA concentration-response curve, and a significant potentiation of the GABA-induced contractions over the lower concentration-range for GABA (3-30 microM). Alfadalone on the other hand, did not affect contractile responses to GABA. 2. Picrotoxinin (10 microM) induced a non-parallel rightward shift of the GABA concentration-response curve, with a 50% depression of the maximum response to GABA. Alfaxalone (100 nM) potentiated the responses to GABA in the presence of picrotoxinin (10 microM) over the GABA concentration-range of 10-100 microM, causing a leftward shift of the concentration-response curve, but without affecting the depression of the maximum response by picrotoxinin. 3. Bicuculline methochloride (10 microM) caused a parallel rightward shift of the GABA concentration-response-curve; the ratio of this shift was unchanged in the presence of alfaxalone (100 microM), although the latter itself displaced the curve leftwards. 4. Alfaxalone (1-100 mM) also induced a similar potentiation of contractile responses to 3-amino-1-propanesulphonic acid (3-APS), a GABA agonist not subject to uptake. Such concentrations of alfaxalone were ineffective against contractile responses to exogenous acetylcholine. 5. Higher concentrations of alfaxalone (1 microM and above), however, elicited a GABA-like ileal contraction, sensitive to both picrotoxinin (10 microM) and bicuculline (10 microM). 6. In conclusion, alfaxalone potentiated GABAA-receptor-mediated contractile responses in the guinea-pig isolated ileum by acting at a modulatory site on GABAA-receptor-chloride-ionophore complexes of GABA-sensitive myenteric neurones, whilst high concentrations of alfaxalone exhibited a GABA-mimetic action at GABAA-receptors in the ileum. It is suggested that more than one site may exist where steroids interact with the GABAA-receptor-ionophore complexes.
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PMID:Alfaxalone potentiates and mimics GABA-induced contractile responses in the guinea-pig isolated ileum. 321 74

The gamma-aminobutyric acid (GABA)-induced contractile responses in the guinea-pig isolated ileum, maintained in Krebs-bicarbonate solution (pH 7.4, 37 degrees C), were significantly potentiated by inhibitors of GABA uptake, with a greater potentiation of the responses in the presence of (+/-)-cis-3-aminocyclohexane-carboxylic acid (ACHC) greater than L-2,4-diaminobutyric acid (DABA) greater than (+/-)-nipecotic acid greater than beta-alanine, whilst simultaneous addition of DABA with beta-alanine caused a greater potentiation of the GABA-induced responses than did nipecotic acid with beta-alanine, or any of the uptake blockers applied alone. The concentration-response curves for the GABA-induced ileal contraction were shifted to the left in the presence of the uptake inhibitors, this shift being more prominent over the lower concentration range of GABA (1-20 microM). By contrast, contractile responses to muscimol or 3-amino-1-propanesulphonic acid (3APS) were not potentiated by the uptake blockers, neither were their concentration-response curves altered. Bicuculline methochloride shifted the GABA concentration-response curve to the right, whilst picrotoxinin both shifted the concentration-response curve for GABA to the right and depressed the maximum response. In the presence of the uptake inhibitors, the rightward shift of the concentration-response curves for GABA induced by bicuculline was less than that induced by bicuculline alone. The rightward shift with picrotoxinin was similarly reduced in the presence of the uptake inhibitors, without altering the depression of the maximum by picrotoxinin. Bicuculline caused a rightward shift of the concentration-response curves for 3APS and muscimol, with the curve for 3APS most affected. Picrotoxinin similarly shifted the concentration-response curves for 3APS and muscimol but depressed the maximum, with the curve for 3APS again being most affected. None of the inhibitors of GABA uptake influenced the concentration-response curves for 3APS or muscimol in the presence of bicuculline or picrotoxinin. 5. In conclusion, a saturable GABA uptake system is present in the enteric nervous system of the guinea-pig intestine, where neuronal GABA uptake appears to predominate over glial uptake.
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PMID:Uptake inhibitors potentiate gamma-aminobutyric acid-induced contractile responses in the isolated ileum of the guinea-pig. 359 86

In isolated segments of guinea-pig small intestine, gamma-aminobutyric acid (GABA) (3-300 microM), the GABAA receptor agonist 3-aminopropane sulphonic acid (3-APS) (3-300 microM) and ivermectin (1-300 microM) caused concentration-dependent nerve-mediated cholinergic contractions sensitive to tetrodotoxin (1 microM) and hyoscine (1 microM). The EC50 values were 30.2 +/- 4.3, 24.6 +/- 3.1 and 4.8 +/- 0.6 microM, respectively. Picrotoxinin (10 microM), an allosteric blocker of the Cl- channel associated with GABAA receptors, non-competitively antagonized the contractile response caused by each agonist. Like picrotoxinin, lindane (10, 30 microM) caused a dose-related shift to the right of the concentration-response curve to GABA, 3-APS and ivermectin with depression of the maximum response. SR 95531 (3 microM), a competitive antagonist of GABAA receptors, caused a parallel dextral shift of the concentration-response curve to ivermectin with an apparent single point pA2 value of 6.5. Our results suggest that ivermectin and lindane, two neurotoxic pesticides interfering with central GABAErgic transmission, exert agonist and non-competitive antagonist properties at the enteric GABAA receptor-ionophore complex. This peripheral complex can thus be considered as an additional target for the action of both these compounds.
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PMID:Interaction of the neurotoxic pesticides ivermectin and lindane with the enteric GABAA receptor-ionophore complex in the guinea-pig. 768 58