Ontogenic aspects of D1 receptor coupling to G proteins and regulation of rat jejunal Na+, K+ ATPase activity and electrolyte transport.
1. The present study examined the effect of dopamine on rat jejunal electrolyte transport (rheogenic transport and Na+, K(+)-ATPase activity) in adult (60-day old) and young (20-day old) animals. 2. In young rats, dopamine, in the presence of phentolamine, produced an increase in jejunal Isc, this being completely abolished by SKF 83566, and not changed by S-sulpiride. SKF 38393, but not quinerolane, also increased Isc; this effect was abolished by SKF 83566 and ouabain, but not by furosemide. In adult rats, dopamine in the presence of phentolamine (0.2 microM) decreased Isc. 3. Na+, K(+)-ATPase activity in isolated jejunal epithelial cells from adult rats was 2.4 fold that in young rats. In the presence of phentolamine, both dopamine and SKF 38393, but not quinerolane, significantly decreased jejunal Na+, K(+)-ATPase activity in young animals but not in adult animals. 4. Binding [3H]-Sch 23390 to membranes of jejunal mucosa revealed the presence of a single class of receptors in both young and adult rats, with similar KD and Bmax values. 5. GTP gamma S and cholera toxin inhibited jejunal Na+, K(+)-ATPase activity in young, but not in adult rats. Co-incubation of pertussis toxin with dopamine was found to potentiate the inhibitory effects of dopamine upon the enzyme in both young and adult rats. 6. Regulation of Na+, K(+)-ATPase activity by cholera toxin-sensitive G proteins is absent in adult animals, and such difference may explain the failure of dopamine to inhibit intestinal Na+, K(+)-ATPase activity in adult rats.
Vieira-Coelho
M A
MA
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004573:Electrolytes / Q000378:metabolism*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007583:Jejunum / Q000201:enzymology* / Q000254:growth & development*; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D004573:Electrolytes; D017447:Receptors, Dopamine D1; D010566:Virulence Factors, Bordetella; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase