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Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea.
Eur J Pharmacol. 2003 Aug 15; 475(1-3):115-8.EJ

Abstract

The effects of cannabinoid receptor agonists on the non-adrenergic non-cholinergic (NANC) inhibitory responses to electrical field stimulation in guinea-pig trachea were assessed. R-(+)-[2,3-dihydro-5-methyl-3-[(morpholilinyl) methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; 10(-5) M) significantly enhanced the frequency-dependent response to electrical stimulation. The same concentration of R-(N)-(2-hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R(+)methanandamide) and 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) did not affect significantly the electrically induced inhibitory NANC responses. The effect of WIN 55,212-2 was not modified by the cannabinoid CB1 and CB2 receptor-selective antagonists, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10(-5) M) and N-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR 144528; 10(-5) M), respectively. Moreover, the nitric oxide synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 10(-4) M), but not the peptidase, alpha-chymotrypsin (2 U/ml), blocked the effect of WIN 55,212-2. Postsynaptically, WIN 55,212-2 did not produce any change of tracheal smooth muscle tone, either basal or histamine-induced, and did not interfere with the relaxant activity of the nitric oxide donor, sodium nitroprusside (10(-8)-10(-4) M). In conclusion, our results suggest that (a) cannabinoid CB1 and CB2 receptor stimulation does not alter the inhibitory NANC transmission in guinea-pig trachea, and (b) WIN 55,212-2 potentiates the NO-mediated component of the NANC relaxant response to electrical stimulation through a cannabinoid receptor-independent mechanism.

Authors+Show Affiliations

Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy. paola.nieri@farm.unipi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12954367

Citation

Nieri, Paola, et al. "Effects of Cannabinoids On Non-adrenergic Non-cholinergic-mediated Relaxation in Guinea-pig Trachea." European Journal of Pharmacology, vol. 475, no. 1-3, 2003, pp. 115-8.
Nieri P, Martinotti E, Testai L, et al. Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea. Eur J Pharmacol. 2003;475(1-3):115-8.
Nieri, P., Martinotti, E., Testai, L., Martinelli, C., & Breschi, M. C. (2003). Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea. European Journal of Pharmacology, 475(1-3), 115-8.
Nieri P, et al. Effects of Cannabinoids On Non-adrenergic Non-cholinergic-mediated Relaxation in Guinea-pig Trachea. Eur J Pharmacol. 2003 Aug 15;475(1-3):115-8. PubMed PMID: 12954367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea. AU - Nieri,Paola, AU - Martinotti,Enrica, AU - Testai,Lara, AU - Martinelli,Cinzia, AU - Breschi,Maria Cristina, PY - 2003/9/5/pubmed PY - 2004/5/5/medline PY - 2003/9/5/entrez SP - 115 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 475 IS - 1-3 N2 - The effects of cannabinoid receptor agonists on the non-adrenergic non-cholinergic (NANC) inhibitory responses to electrical field stimulation in guinea-pig trachea were assessed. R-(+)-[2,3-dihydro-5-methyl-3-[(morpholilinyl) methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; 10(-5) M) significantly enhanced the frequency-dependent response to electrical stimulation. The same concentration of R-(N)-(2-hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R(+)methanandamide) and 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) did not affect significantly the electrically induced inhibitory NANC responses. The effect of WIN 55,212-2 was not modified by the cannabinoid CB1 and CB2 receptor-selective antagonists, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10(-5) M) and N-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR 144528; 10(-5) M), respectively. Moreover, the nitric oxide synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 10(-4) M), but not the peptidase, alpha-chymotrypsin (2 U/ml), blocked the effect of WIN 55,212-2. Postsynaptically, WIN 55,212-2 did not produce any change of tracheal smooth muscle tone, either basal or histamine-induced, and did not interfere with the relaxant activity of the nitric oxide donor, sodium nitroprusside (10(-8)-10(-4) M). In conclusion, our results suggest that (a) cannabinoid CB1 and CB2 receptor stimulation does not alter the inhibitory NANC transmission in guinea-pig trachea, and (b) WIN 55,212-2 potentiates the NO-mediated component of the NANC relaxant response to electrical stimulation through a cannabinoid receptor-independent mechanism. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/12954367/Effects_of_cannabinoids_on_non_adrenergic_non_cholinergic_mediated_relaxation_in_guinea_pig_trachea_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299903021228 DB - PRIME DP - Unbound Medicine ER -