Stimulation of mucosal alkaline secretion in rat duodenum by dopamine and 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.
Flemström
G
G
Department of Physiology and Medical Biophysics, Uppsala University Biomedical Center, Sweden.
Säfsten
B
B
Jedstedt
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004381:Duodenal Ulcer / Q000517:prevention & control; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010422:Pentanones / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D015259:Dopamine Agents; D006584:Hexamethonium Compounds; D010422:Pentanones; D018738:Hexamethonium; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C057364:nitecapone; D004298:Dopamine; D010646:Phentolamine