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Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig.
Basic Clin Pharmacol Toxicol. 2006 May; 98(5):488-95.BC

Abstract

Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the gastrointestinal tract. The present study examined the motor effects of exogenous ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and the influence of drugs on the ATP-induced responses. High micromolar concentrations of ATP caused two types of contraction, a phasic, cholinergic response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M, respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M) caused guanethidine-resistant relaxation. This response was not influenced by tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5) M), in a surmountable manner. A high degree of tachyphylaxis was observed with the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M) of PPADS failed to influence ileum contractions to exogenous acetylcholine or histamine. It is concluded that, in addition to its direct contractile action in the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic neurones, an effect whose mechanism is largely different from that of alpha,beta-methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor-mediated effect on the smooth muscle. All motor effects of ATP are inhibited by the antagonist PPADS.

Authors+Show Affiliations

Department of Pharmacology and Pharmacotherapy, Division of Pharmacodynamics, University of Pécs Medical School, Pécs, Hungary. Lorand.Bartho@aok.pte.huNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16635108

Citation

Barthó, Lorand, et al. "Multiple Motor Effects of ATP and Their Inhibition By P Purinoceptor Antagonist, Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic Acid in the Small Intestine of the Guinea-pig." Basic & Clinical Pharmacology & Toxicology, vol. 98, no. 5, 2006, pp. 488-95.
Barthó L, Undi S, Benkó R, et al. Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig. Basic Clin Pharmacol Toxicol. 2006;98(5):488-95.
Barthó, L., Undi, S., Benkó, R., Wolf, M., Lázár, Z., Lénárd, L., & Maggi, C. A. (2006). Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig. Basic & Clinical Pharmacology & Toxicology, 98(5), 488-95.
Barthó L, et al. Multiple Motor Effects of ATP and Their Inhibition By P Purinoceptor Antagonist, Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic Acid in the Small Intestine of the Guinea-pig. Basic Clin Pharmacol Toxicol. 2006;98(5):488-95. PubMed PMID: 16635108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig. AU - Barthó,Lorand, AU - Undi,Sarolta, AU - Benkó,Rita, AU - Wolf,Matyas, AU - Lázár,Zsofia, AU - Lénárd,Laszlo,Jr AU - Maggi,Carlo A, PY - 2006/4/26/pubmed PY - 2006/12/9/medline PY - 2006/4/26/entrez SP - 488 EP - 95 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin. Pharmacol. Toxicol. VL - 98 IS - 5 N2 - Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the gastrointestinal tract. The present study examined the motor effects of exogenous ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and the influence of drugs on the ATP-induced responses. High micromolar concentrations of ATP caused two types of contraction, a phasic, cholinergic response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M, respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M) caused guanethidine-resistant relaxation. This response was not influenced by tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5) M), in a surmountable manner. A high degree of tachyphylaxis was observed with the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M) of PPADS failed to influence ileum contractions to exogenous acetylcholine or histamine. It is concluded that, in addition to its direct contractile action in the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic neurones, an effect whose mechanism is largely different from that of alpha,beta-methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor-mediated effect on the smooth muscle. All motor effects of ATP are inhibited by the antagonist PPADS. SN - 1742-7835 UR - https://www.unboundmedicine.com/medline/citation/16635108/Multiple_motor_effects_of_ATP_and_their_inhibition_by_P_purinoceptor_antagonist_pyridoxalphosphate_6_azophenyl_2'4'_disulphonic_acid_in_the_small_intestine_of_the_guinea_pig_ L2 - https://doi.org/10.1111/j.1742-7843.2006.pto_369.x DB - PRIME DP - Unbound Medicine ER -