Histamine (HA) contracts gastrointestinal smooth muscle cells from both animals and humans through the activation of H1 receptors. The recent discovery of the H4 receptor subtype, causing a rise in the intracellular Ca2+ levels and then representing a potential mechanism of contraction, prompted us to re-investigate the effects of HA on the human intestinal motility. The effects of HA were tested on intestinal strips, taken from human colonic or ileal specimens excised during intestinal surgery. In such preparations, the effects of HA and of HA receptor antagonists were evaluated for their ability to modify the basal tone and spontaneous motility. HA (10 nM-100 µM) induced a transient relaxation, followed by a tonic contraction of longitudinal muscle preparations from both ileal and colonic strips. The effects of HA were refractory to H2, H3 and H4 receptor blockade by famotidine (1 µM), FUB649 (1 µM) or compound JNJ 7777120 (1 µM), respectively, but counteracted by the H1-receptor antagonists, mepyramine and chlorphenyramine, in the same range of concentration (1 nM-1 µM). The effects of HA could not be reproduced by the specific H1-receptor agonist, 2-(3-trifluoromethylphenyl)histamine. Tetrodotoxin (1 µM), propranolol (1 µM) and L-NAME (100 µM) did not cause any significant modification of the HA-induced inhibitory response, excluding the involvement of inhibitory adrenergic or NANC neurons or the activation of nitric oxide (NO)-producing cells. The response of the human intestinal muscle to HA is related to the activation of H1 receptors, which mediate both excitatory and inhibitory effects in both colon and ileum. No evidence of functional histamine H4 receptors in the human intestine could be provided. The so far unexplored H1-mediated inhibition is independent of substances released from the intramural nerves and of NO spillover from cells resident into the intestinal wall. Other autacoids (inhibitory prostaglandins and/or purinergic transmitters), or the activation of K+ fluxes in muscle cells could be involved.
Dualistic H1-mediated effect of histamine on the isolated human intestine / Poli, Enzo; Pozzoli, Cristina; Regina, C.; Menozzi, Alessandro; Roncoroni, Luigi; Coruzzi, G.. - In: INFLAMMATION RESEARCH. - ISSN 1023-3830. - 55:(2006), pp. 65-66. [10.1007/s00011-005-0045-x]
Dualistic H1-mediated effect of histamine on the isolated human intestine.
POLI, Enzo;POZZOLI, Cristina;MENOZZI, Alessandro;RONCORONI, Luigi;
2006-01-01
Abstract
Histamine (HA) contracts gastrointestinal smooth muscle cells from both animals and humans through the activation of H1 receptors. The recent discovery of the H4 receptor subtype, causing a rise in the intracellular Ca2+ levels and then representing a potential mechanism of contraction, prompted us to re-investigate the effects of HA on the human intestinal motility. The effects of HA were tested on intestinal strips, taken from human colonic or ileal specimens excised during intestinal surgery. In such preparations, the effects of HA and of HA receptor antagonists were evaluated for their ability to modify the basal tone and spontaneous motility. HA (10 nM-100 µM) induced a transient relaxation, followed by a tonic contraction of longitudinal muscle preparations from both ileal and colonic strips. The effects of HA were refractory to H2, H3 and H4 receptor blockade by famotidine (1 µM), FUB649 (1 µM) or compound JNJ 7777120 (1 µM), respectively, but counteracted by the H1-receptor antagonists, mepyramine and chlorphenyramine, in the same range of concentration (1 nM-1 µM). The effects of HA could not be reproduced by the specific H1-receptor agonist, 2-(3-trifluoromethylphenyl)histamine. Tetrodotoxin (1 µM), propranolol (1 µM) and L-NAME (100 µM) did not cause any significant modification of the HA-induced inhibitory response, excluding the involvement of inhibitory adrenergic or NANC neurons or the activation of nitric oxide (NO)-producing cells. The response of the human intestinal muscle to HA is related to the activation of H1 receptors, which mediate both excitatory and inhibitory effects in both colon and ileum. No evidence of functional histamine H4 receptors in the human intestine could be provided. The so far unexplored H1-mediated inhibition is independent of substances released from the intramural nerves and of NO spillover from cells resident into the intestinal wall. Other autacoids (inhibitory prostaglandins and/or purinergic transmitters), or the activation of K+ fluxes in muscle cells could be involved.File | Dimensione | Formato | |
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