Dopamine and vasoactive intestinal peptide stimulate cyclic adenosine-3',5'-monophosphate formation in isolated rat villus and crypt duodenocytes.
Secretion of bicarbonate increases the pH at the duodenal mucosal surface, a process which contributes to the protection against acid/pepsin injury. Previously, we have shown that dopaminergic compounds stimulate the duodenal bicarbonate secretion in situ, in the anaesthetized rat, through an action on peripheral dopamine D1 receptors. In order to study the possible involvement of cyclic adenosine-3',5'-monophosphate (cAMP) as an intracellular mediator in enterocytes isolated from rat duodenum, cells were collected by a combination of enzyme treatment and calcium chelation. Two major cell fractions, one mainly from villi and the other mainly of crypt origin, were studied. In the villus cell fraction, the activity of alkaline phosphatase was 1.6 +/- 0.2 mumol mg protein-1 min-1 and that of sucrase 98.8 +/- 16.4 nmol mg protein-1 min-1. In the crypt fraction, activities were 0.7 +/- 0.1 and 28 +/- 10.5, respectively. Effects of dopamine, two selective dopamine receptor agonists and vasoactive intestinal peptide (VIP) on intracellular accumulation of cAMP were examined by radio-immunoassay (RIA). In the crypt cell fraction, VIP (10(-7) M) caused an increase in cAMP which was maximal after 5 min (78 +/- 28% above control, P < 0.01). In the villus cell fraction, maximal responses to VIP (60 +/- 24% above control, P < 0.05), did not occur until after 60 min of incubation. In contrast, there were no significant differences between villi and crypt enterocytes in respect to effects of dopamine, the dopamine D1-receptor agonist SKF-38393 and the D2-receptor agonist quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)
Säfsten
B
B
Department of Physiology and Medical Biophysics, Uppsala University Biomedical Centre, Sweden.
Flemström
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004386:Duodenum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019257:Quinpirole; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013393:Sucrase / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D015259:Dopamine Agents; D004873:Ergolines; D019257:Quinpirole; D014660:Vasoactive Intestinal Peptide; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D013393:Sucrase; D004298:Dopamine