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Abstract

Coexistence of histamine H1 and H2 receptors coupled to distinct signal transduction pathways in isolated intestinal muscle cells.

G Morini, J F Kuemmerle, M Impicciatore, J R Grider and G M Makhlouf
Journal of Pharmacology and Experimental Therapeutics February 1993, 264 (2) 598-603;
G Morini
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J F Kuemmerle
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M Impicciatore
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J R Grider
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G M Makhlouf
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Abstract

Histamine receptors were characterized in muscle cells isolated from the longitudinal muscle layer of guinea pig intestine. Histamine caused concentration-dependent contraction and stimulated significant increases in [Ca++]i (141 +/- 16 nM, P < .001) and cyclic AMP (cAMP) (10.3 +/- 0.5 pmol/10(6) cells, P < .001). The H1 receptor antagonist, mepyramine, inhibited contraction and the increase in [Ca++]i, whereas the H2 receptor antagonist, cimetidine, augmented contraction and the increase in [Ca++]i (277 +/- 31 nM, P < .01) and abolished the increase in cAMP. In cells maximally contracted with a nonhistamine agonist [cholecystokinin octapeptide (CCK)], histamine caused concentration-dependent relaxation when the contractile effect mediated by H1 receptors was blocked with mepyramine; relaxation was inhibited by cimetidine in a concentration-dependent fashion. The effects mediated by H1 and H2 receptors were characterized further in cells in which only one receptor type was preserved by selective receptor protection. In cells in which only H1 receptors were preserved, histamine caused contraction that was inhibited by mepyramine; no relaxation of CCK-induced contraction could be elicited by histamine in the presence of mepyramine. Conversely, in cells in which only H2 receptors were preserved, histamine had little or no contractile effect by itself but caused relaxation of CCK-induced contraction in the absence of mepyramine. We conclude that in, intestinal muscle cells, H1 receptors mediating Ca(++)-dependent contraction coexist with H2 receptors mediating cAMP-dependent relaxation. The effect of histamine reflects activation of dominant H1 receptors as well as of H2 receptors which act to attenuate [Ca++]i and contraction by stimulating an increase in intracellular cAMP.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 264, Issue 2
1 Feb 1993
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Abstract

Coexistence of histamine H1 and H2 receptors coupled to distinct signal transduction pathways in isolated intestinal muscle cells.

G Morini, J F Kuemmerle, M Impicciatore, J R Grider and G M Makhlouf
Journal of Pharmacology and Experimental Therapeutics February 1, 1993, 264 (2) 598-603;

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Abstract

Coexistence of histamine H1 and H2 receptors coupled to distinct signal transduction pathways in isolated intestinal muscle cells.

G Morini, J F Kuemmerle, M Impicciatore, J R Grider and G M Makhlouf
Journal of Pharmacology and Experimental Therapeutics February 1, 1993, 264 (2) 598-603;
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