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Abstract

Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype.

J P Trzeciakowski
Journal of Pharmacology and Experimental Therapeutics December 1987, 243 (3) 874-880;
J P Trzeciakowski
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Abstract

Segments of guinea pig ileum were isolated and placed on coaxial electrodes in organ baths filled with oxygenated Krebs' solution at 37 degrees C. Twitch responses were produced with rectangular-wave stimuli (0.5 msec; 10 Hz; 4.8-12 V) delivered in 1-sec trains every 10 sec. After addition of pyrilamine to block H1-mediated contractions, histamine and N alpha-methylhistamine (NMH) inhibited the twitch responses with EC50 values of 64 and 1.7 nM, respectively. In contrast, there was no difference in potency between histamine and NMH at contractile H1 receptors in ileum longitudinal muscle or at chronotropic H2 receptors in the atria. Impromidine blocked the inhibitory effect of NMH in a competitive manner with a KB value of 26 nM, whereas inhibition caused by gamma-aminobutyric acid or by adenosine remained unaffected by impromidine. At concentrations that completely prevented the electrically induced twitch, NMH did not alter contractions produced by exogenous acetylcholine. Inhibitory responses to NMH were unaffected by cimetidine, hexamethonium, combined alpha and beta adrenergic receptor blockade, naloxone, 8-phenyltheophylline or gamma-aminobutyric acid receptor desensitization. These data support the presence of inhibitory histamine receptors in the ileum that are pharmacologically similar to the presynaptic H3 autoreceptors found in rat cortex. The distribution of H3 receptors, therefore, may not be confined to the central nervous system and their function, as with alpha-2 adrenergic sites, may not be limited to that of an autoreceptor.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 243, Issue 3
1 Dec 1987
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Abstract

Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype.

J P Trzeciakowski
Journal of Pharmacology and Experimental Therapeutics December 1, 1987, 243 (3) 874-880;

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Abstract

Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype.

J P Trzeciakowski
Journal of Pharmacology and Experimental Therapeutics December 1, 1987, 243 (3) 874-880;
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