G Flemström1, B Säfsten, G Jedstedt. 1. Department of Physiology and Medical Biophysics, Uppsala University Biomedical Center, Sweden.
Abstract
BACKGROUND: The catechol-O-methyl-transferase (COMT) inhibitor nitecapone, which prevents mucosal degradation of dopamine, and some dopamine receptor agonists ameliorate gastroduodenal mucosal damage. Therefore, their effects on mucosal bicarbonate secretion were studied. METHODS: Duodenum just distal to the Brunner's glands area was cannulated in situ in anesthetized rats. Bicarbonate secretion into the luminal perfusate and transmucosal electrical potential difference (PD) were recorded. RESULTS: Intravenous dopamine (50 micrograms.kg-1 x h-1) increased bicarbonate secretion twofold, and a higher rate of infusion (250 micrograms.kg-1 x h-1) resulted in a further increase. Neither dose affected the PD. The dopamine D1 agonist SKF-38393 (10-50 micrograms/kg) and the COMT inhibitor nitecapone (50-500 micrograms/kg) caused dose-dependent increases in secretion, similar to that observed with dopamine. Domperidone, a peripherally acting dopamine antagonist, inhibited the stimulatory effects of SKF-38393 and nitecapone. Hexamethonium or the alpha-adrenoceptor antagonist phentolamine, in contrast, did not affect the response to nitecapone. Intracerebroventricular administration of nitecapone was without effect. CONCLUSIONS: A probable electroneutral component of duodenal mucosal bicarbonate secretion is stimulated via peripheral dopamine D1 receptors. This may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.
BACKGROUND: The catechol-O-methyl-transferase (COMT) inhibitor nitecapone, which prevents mucosal degradation of dopamine, and some dopamine receptor agonists ameliorate gastroduodenal mucosal damage. Therefore, their effects on mucosal bicarbonate secretion were studied. METHODS: Duodenum just distal to the Brunner's glands area was cannulated in situ in anesthetized rats. Bicarbonate secretion into the luminal perfusate and transmucosal electrical potential difference (PD) were recorded. RESULTS: Intravenous dopamine (50 micrograms.kg-1 x h-1) increased bicarbonate secretion twofold, and a higher rate of infusion (250 micrograms.kg-1 x h-1) resulted in a further increase. Neither dose affected the PD. The dopamine D1 agonist SKF-38393 (10-50 micrograms/kg) and the COMT inhibitor nitecapone (50-500 micrograms/kg) caused dose-dependent increases in secretion, similar to that observed with dopamine. Domperidone, a peripherally acting dopamine antagonist, inhibited the stimulatory effects of SKF-38393 and nitecapone. Hexamethonium or the alpha-adrenoceptor antagonist phentolamine, in contrast, did not affect the response to nitecapone. Intracerebroventricular administration of nitecapone was without effect. CONCLUSIONS: A probable electroneutral component of duodenal mucosal bicarbonate secretion is stimulated via peripheral dopamine D1 receptors. This may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.
Authors: Abdulrahman Al Asmari; Mohammed Arshaduddin; Ibrahim Elfaki; Saeed Kadasah; Abdulrahman Al Robayan; Saeed Al Asmary Journal: Int J Clin Exp Med Date: 2014-08-15