Strips of guinea-pig ileum (8 x 2 mm) were superfused (Krebs, 37 degrees C, 2 ml min-1) with: (i) tachykinin receptor agonists: SP, GR 73,632 (NK1), GR 64,349 (NK2), senktide (NK3), and neuropeptide (NP) gamma; (ii) tachykinin receptor antagonists: CP 99,994 (NK1), SR 48,968 (NK2), SR 142,801 (NK3); (iii) nerve-related brokers: carbachol (CCh), atropine, tetrodotoxin (TTX), hexamethonium; (iv) NOS inhibitors: N omega-nitro-L-arginine-methyl-ester (L-NAME), N omega-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG); (v) NO-related brokers, L-arginine (L-Arg), D-arginine (D-Arg), sodium nitroprusside (NaNP) and methaemoglobin. area of activity. 3. SP, tachykinin receptor agonists and NP gamma (10 pM to 10 microM), produced concentration-dependent contractions of ileal strips, with EC50s in the nanomolar range, and maximal responses (Emax) achieved at 0.1 microM for SP and 1 microM for the other agonists. The Emax response to SP equalled that to KCl (60 mM) taken as a 100% control (99.3% [93.0-105.7]; mean and 95% CI; n = 12); a comparable Emax contraction was obtained with the other tachykinin receptor agonists (1 microM) as well as with CCh (1 microM). 4. Under baseline conditions, L-NAME (1 microM), L-NMMA (1 microM) and AG (1 microM), failed to contract the muscle mass strip. In contrast, when superfused for 3 min, 10 min after SP (0.1 microM), they induced a transient contraction of the strip (e.g. for 1 microM L-NAME: 50 to 70 s period; amplitude 73 +/- 12%, n = 24). 5. The NOS inhibitor-induced contractile response was not obtained after KCl (60 mM), GR 73,632, GR 64,349, senktide or CCh (all up to 1 1 microM). In contrast, this contractile response was obtained after NP gamma (1 microM). 6. Blockade of tachykinin NK1, NK2 and NK3 receptors by continuous superfusion of CP 99,994, SR 48,968 and SR 142,801 (1 microM) respectively, starting 5 min before SP, did not change the response to L-NAME, superfused 10 min after SP (0.1 microM). The contractile response to L-NAME (1 microM) was blocked by atropine (1 microM), superfused either before or after SP. In contrast, it persisted after TTX or hexamethonium (1 microM) superfused in the same conditions. 7. The amplitude of NOS inhibitor-induced contraction (1 microM) was dependent on the concentration of priming SP (1 pM to 1 1 microM). In contrast, the contractile response to NOS inhibitors (1 nM to 10 microM) of the ileum strip primed with SP (0.1 microM) was not concentration-related. 8. L-NAME-induced contraction was Prinaberel prevented by continuous superfusion of L-Arg (1 microM), but not D-Arg (1 microM). In addition, the NO donor, sodium nitroprusside (1 microM) and the NO scavenger, methaemoglobin (10 micrograms ml-1), both prevented the contractile response to L-NAME. 9. In summary, SP and to a lesser extent NP gamma, exert a permissive action allowing contractile stimulating effects of L-NAME, L-NMMA and AG, in guinea-pig ileum in vitro, by a mechanism which apparently does not involve tachykinin NK1, NK2 and NK3 receptors. This action is likely to result from the activation of a NO-synthase by SP in the vicinity of intestinal myocytes. Thus, L-NAME, L-NMMA or AG, by blocking this SP-induced NO production, unveiled a easy muscle contraction which involves a cholinoceptor (atropine-sensitive) mechanism. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected Recommendations. ? 1253 1254 1255 1256 1257 1258 1259 1260 1261 ? Images in this article Physique 6
on p.1259 Click on the image to see a larger version. Selected.3. integrated area of activity. 3. SP, tachykinin receptor agonists and NP gamma (10 pM to 10 microM), produced concentration-dependent contractions of ileal strips, with EC50s in the nanomolar range, and maximal responses (Emax) achieved at 0.1 microM for SP and 1 microM for the other agonists. The Emax response to SP equalled that to KCl (60 mM) taken as a 100% control (99.3% [93.0-105.7]; mean and 95% CI; n = 12); a comparable Emax contraction was obtained with the other tachykinin receptor agonists (1 microM) as well as with CCh (1 microM). 4. Under baseline conditions, L-NAME (1 microM), L-NMMA (1 microM) and AG (1 microM), failed to contract the muscle mass strip. In contrast, when superfused for 3 min, 10 min after SP (0.1 microM), they induced a transient contraction of the strip (e.g. for 1 microM L-NAME: 50 to 70 s period; amplitude 73 +/- 12%, n = 24). 5. The NOS inhibitor-induced contractile response was not obtained after KCl (60 mM), GR 73,632, GR 64,349, senktide or CCh (all up to 1 1 microM). In contrast, this contractile response was obtained after NP gamma (1 microM). 6. Blockade of tachykinin NK1, NK2 and NK3 receptors by continuous superfusion of CP 99,994, SR 48,968 and SR 142,801 (1 microM) respectively, starting 5 min before SP, did not change the response to L-NAME, superfused 10 min after SP (0.1 microM). The contractile response to L-NAME (1 microM) was blocked by atropine (1 microM), superfused either before or after SP. In contrast, it persisted after TTX or hexamethonium (1 microM) superfused in the same conditions. 7. The amplitude of NOS inhibitor-induced contraction (1 microM) was dependent on the concentration of priming SP (1 pM to 1 1 microM). In contrast, the contractile response to NOS inhibitors (1 nM to 10 microM) of the ileum strip primed with SP (0.1 microM) was not concentration-related. 8. L-NAME-induced contraction was prevented by continuous superfusion of L-Arg (1 microM), but not D-Arg (1 microM). In addition, the NO donor, sodium nitroprusside (1 microM) and the NO scavenger, methaemoglobin (10 micrograms ml-1), both avoided the contractile response to L-NAME. 9. In conclusion, SP also to a lesser level NP gamma, exert a permissive actions enabling contractile stimulating ramifications of L-NAME, L-NMMA and AG, in guinea-pig ileum in vitro, with a system which evidently will not involve tachykinin NK1, NK2 and NK3 receptors. This step will probably derive from the activation of the NO-synthase by SP near intestinal myocytes. Hence, L-NAME, L-NMMA or AG, by preventing this SP-induced NO creation, unveiled a simple muscle contraction that involves a cholinoceptor (atropine-sensitive) system. Full text Total text is obtainable being a scanned duplicate of the initial print version. Get yourself a printable duplicate (PDF document) of the entire content (1.8M), or select a page picture below to browse web page by web page. Links to PubMed may also be designed for Selected Sources. ? 1253 1254 1255 1256 1257 1258 1259 1260 1261 ? Pictures in this specific article Body 6
on p.1259 Go through the picture to visit a bigger version. Selected.SP, tachykinin receptor agonists and NP gamma (10 pM to 10 microM), produced concentration-dependent contractions of ileal whitening strips, with EC50s in the nanomolar range, and maximal replies (Emax) attained in 0.1 microM for SP and 1 microM for the various other agonists. (L-NAME), N omega-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG); (v) NO-related agencies, L-arginine (L-Arg), D-arginine (D-Arg), sodium nitroprusside (NaNP) and methaemoglobin. Muscle tissue contractility was recorded and quantified seeing that integrated section of activity isometrically. 3. SP, tachykinin receptor agonists and NP gamma (10 pM to 10 microM), created concentration-dependent contractions of ileal whitening strips, with EC50s in the nanomolar range, and maximal replies (Emax) obtained at 0.1 microM for SP and 1 microM for the various other agonists. The Emax response to SP equalled that to KCl (60 mM) used as a 100% control (99.3% [93.0-105.7]; mean and 95% CI; n = 12); a equivalent Emax contraction was attained using the various other tachykinin receptor agonists (1 microM) aswell much like CCh (1 microM). 4. Under baseline circumstances, L-NAME (1 microM), L-NMMA (1 microM) and AG (1 microM), didn’t contract the muscle tissue remove. On the other hand, when superfused for 3 min, 10 min after SP (0.1 microM), they induced a transient contraction from the strip (e.g. for 1 microM L-NAME: 50 to 70 s length; amplitude 73 +/- 12%, n = 24). 5. The NOS inhibitor-induced contractile response had not been attained after KCl (60 mM), GR 73,632, GR 64,349, senktide or CCh (all up to at least one 1 microM). On the other hand, this contractile response was attained after NP gamma (1 microM). 6. Blockade of tachykinin NK1, NK2 and NK3 receptors by constant superfusion of CP 99,994, SR 48,968 and SR 142,801 (1 microM) respectively, beginning 5 min before SP, didn’t enhance the response to L-NAME, superfused 10 min after SP (0.1 microM). The contractile response to L-NAME (1 microM) was obstructed by atropine (1 microM), superfused either before or after SP. On the other hand, it persisted after TTX or hexamethonium (1 microM) superfused in the same circumstances. 7. The amplitude of NOS inhibitor-induced contraction (1 microM) was reliant on the focus of priming SP (1 pM to at least one 1 microM). On the other hand, the contractile response to NOS inhibitors (1 nM to 10 microM) from the ileum remove primed with SP (0.1 microM) had not been concentration-related. 8. L-NAME-induced contraction was avoided by constant superfusion of L-Arg (1 microM), however, not D-Arg (1 microM). Furthermore, the NO donor, sodium nitroprusside (1 microM) as well as the NO scavenger, methaemoglobin (10 micrograms ml-1), both avoided the contractile response to L-NAME. 9. In conclusion, SP also to a lesser level NP gamma, exert a permissive actions enabling contractile stimulating ramifications of L-NAME, L-NMMA and AG, in guinea-pig ileum in vitro, with a system which evidently will not involve tachykinin NK1, NK2 and NK3 receptors. This step will probably derive from the activation of the NO-synthase by SP near intestinal myocytes. Hence, L-NAME, L-NMMA or AG, by preventing this SP-induced NO creation, unveiled a simple muscle contraction that involves a cholinoceptor (atropine-sensitive) system. Full text Total text is obtainable being a scanned duplicate of Prinaberel the Prinaberel initial print version. Get yourself a printable duplicate (PDF document) of the entire content (1.8M), or select a page picture below to browse web page by web page. Links to PubMed may also be designed for Selected Sources. ? 1253 1254 1255 1256 1257 1258 1259 1260 1261 ? Pictures in this specific article Body 6
on p.1259 Go through the picture to visit a bigger version. Selected.Furthermore, the Zero donor, sodium nitroprusside (1 microM) as well as the Zero scavenger, methaemoglobin (10 micrograms ml-1), both prevented the contractile response to L-NAME. D-arginine (D-Arg), sodium nitroprusside (NaNP) and methaemoglobin. Muscle tissue contractility was documented isometrically and quantified as integrated section of activity. 3. SP, tachykinin receptor agonists and NP gamma (10 pM to 10 microM), created concentration-dependent contractions of ileal whitening strips, with EC50s in the nanomolar range, and maximal replies (Emax) obtained at 0.1 microM for SP and 1 microM for the various other agonists. The Emax response to SP equalled that to KCl (60 mM) used as a 100% control (99.3% [93.0-105.7]; mean and 95% CI; n = 12); a equivalent Emax contraction was attained using the various other tachykinin receptor agonists (1 microM) aswell much like CCh (1 microM). 4. Under baseline circumstances, L-NAME (1 microM), L-NMMA (1 microM) and AG (1 microM), didn’t contract the muscle tissue remove. On the other hand, when superfused for 3 min, 10 min after SP (0.1 microM), they induced a transient contraction from the strip (e.g. for 1 microM L-NAME: 50 to 70 s length; amplitude 73 +/- 12%, n = 24). 5. The NOS inhibitor-induced contractile response had not been attained after KCl (60 mM), GR 73,632, GR 64,349, senktide or CCh (all up to at least one 1 microM). On the other hand, this contractile response was attained after NP gamma (1 microM). 6. Blockade of tachykinin NK1, NK2 and NK3 receptors by constant superfusion of CP 99,994, SR 48,968 and SR 142,801 (1 microM) respectively, beginning 5 min before SP, didn’t enhance the response to L-NAME, superfused 10 min after SP (0.1 microM). The contractile response to L-NAME (1 microM) was obstructed by atropine (1 microM), superfused either before S5mt or after SP. On the other hand, it persisted after TTX Prinaberel or hexamethonium (1 microM) superfused in the same circumstances. 7. The amplitude of NOS inhibitor-induced contraction (1 microM) was reliant on the focus of priming SP (1 pM to at least one 1 microM). On the other hand, the contractile response to NOS inhibitors (1 nM to 10 microM) from the ileum remove primed with SP (0.1 microM) had not been concentration-related. 8. L-NAME-induced contraction was avoided by constant superfusion of L-Arg (1 microM), however, not D-Arg (1 microM). Furthermore, the NO donor, sodium nitroprusside (1 microM) as well as the NO scavenger, methaemoglobin (10 micrograms ml-1), both avoided the contractile response to L-NAME. 9. In conclusion, SP also to a lesser level NP gamma, exert a permissive actions enabling contractile stimulating ramifications of L-NAME, L-NMMA and AG, in guinea-pig ileum in vitro, with a system which evidently will not involve tachykinin NK1, NK2 and NK3 receptors. This step will probably derive from the activation of the NO-synthase by SP near intestinal myocytes. Hence, L-NAME, L-NMMA or AG, by preventing this SP-induced NO creation, unveiled a simple muscle contraction that involves a cholinoceptor (atropine-sensitive) system. Full text Total text is obtainable being a scanned duplicate of the initial print version. Get yourself a printable duplicate (PDF document) of the entire content (1.8M), or select a page picture below to browse web page by page. Links to PubMed are also available for Selected References. ? 1253 1254 1255 1256 1257 1258 1259 1260 1261 ? Images in this article Figure 6
on p.1259 Click on the image to see a larger version. Selected.The amplitude of NOS inhibitor-induced contraction (1 microM) was dependent on the concentration of priming SP (1 pM to 1 1 microM). gamma (10 pM to 10 microM), produced concentration-dependent contractions of ileal strips, with EC50s in the nanomolar range, and maximal responses (Emax) attained at 0.1 microM for SP and 1 microM for the other agonists. The Emax response to SP equalled that to KCl (60 mM) taken as a 100% control (99.3% [93.0-105.7]; mean and 95% CI; n = 12); a comparable Emax contraction was obtained with the other tachykinin receptor agonists (1 microM) as well as with CCh (1 microM). 4. Under baseline conditions, L-NAME (1 microM), L-NMMA (1 microM) and AG (1 microM), failed to contract the muscle strip. In contrast, when superfused for 3 min, 10 min after SP (0.1 microM), they induced a transient contraction of the strip (e.g. for 1 microM L-NAME: 50 to 70 s duration; amplitude 73 +/- 12%, n = 24). 5. The NOS inhibitor-induced contractile response was not obtained after KCl (60 mM), GR 73,632, GR 64,349, senktide or CCh (all up to 1 1 microM). In contrast, this contractile response was obtained after NP gamma (1 microM). 6. Blockade of tachykinin NK1, NK2 and NK3 receptors by continuous superfusion of CP 99,994, SR 48,968 and SR 142,801 (1 microM) respectively, starting 5 min before SP, did not modify the response to L-NAME, superfused 10 min after SP (0.1 microM). The contractile response to L-NAME (1 microM) was blocked by atropine (1 microM), superfused either before or after SP. In contrast, it persisted after TTX or hexamethonium (1 microM) superfused in the same conditions. 7. The amplitude of NOS inhibitor-induced contraction (1 microM) was dependent on the concentration of priming SP (1 pM to 1 1 microM). In contrast, the contractile response to NOS inhibitors (1 nM to 10 microM) of Prinaberel the ileum strip primed with SP (0.1 microM) was not concentration-related. 8. L-NAME-induced contraction was prevented by continuous superfusion of L-Arg (1 microM), but not D-Arg (1 microM). In addition, the NO donor, sodium nitroprusside (1 microM) and the NO scavenger, methaemoglobin (10 micrograms ml-1), both prevented the contractile response to L-NAME. 9. In summary, SP and to a lesser extent NP gamma, exert a permissive action allowing contractile stimulating effects of L-NAME, L-NMMA and AG, in guinea-pig ileum in vitro, by a mechanism which apparently does not involve tachykinin NK1, NK2 and NK3 receptors. This action is likely to result from the activation of a NO-synthase by SP in the vicinity of intestinal myocytes. Thus, L-NAME, L-NMMA or AG, by blocking this SP-induced NO production, unveiled a smooth muscle contraction which involves a cholinoceptor (atropine-sensitive) mechanism. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. ? 1253 1254 1255 1256 1257 1258 1259 1260 1261 ? Images in this article Figure 6
on p.1259 Click on the image to see a larger version. Selected.