Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum
The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to all doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.
- Research Organization:
- Louisiana State Univ. Medical Center, New Orleans
- OSTI ID:
- 5614617
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
METRONIDAZOLE
BIOLOGICAL EFFECTS
SALICYLIC ACID
COMPUTERS
CONTRACTION
DOSE-RESPONSE RELATIONSHIPS
GUINEA PIGS
HEART
HISTAMINE
IN VITRO
RECEPTORS
SMALL INTESTINE
ALCOHOLS
AMINES
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
DIGESTIVE SYSTEM
DRUGS
GASTROINTESTINAL TRACT
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
IMIDAZOLES
INTESTINES
MAMMALS
MEMBRANE PROTEINS
NITRO COMPOUNDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
RADIOSENSITIZERS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)