Alpha2-adrenoceptors mediate the effect of dopamine on adult rat jejunal electrolyte transport.
The present study was aimed to characterise the effect of dopamine on rat jejunal electrolyte transport and to evaluate the type of receptors and the intracellular signalling mechanisms involved in the response. Stripped epithelial sheets were mounted in Ussing chambers connected to an automatic voltage current clamp and changes in the short circuit current (microA/cm2) were measured continuously as an index of electrogenic ion transfer. Dopamine (0.1-100 microM) produced a concentration dependent decrease in Isc with an EC50 of 1.4+/-0.1 microM: the effect of dopamine was not changed by propranolol (1 microM), prazosin (1 microM and 10 microM) or (+/-)-sulpiride (1 microM). but was completely abolished by phentolamine (1 microM). The addition of phentolamine (0.3 microM) or yohimbine (0.3 microM) produced a rightward shift of the dopamine concentration-dependent curve with an increase in EC50 values up to 30.0+/-0.2 microM and 11.7+/-0.1 microM. respectively. The alpha2-adrenoceptor-selective agonist, UK14,304 (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine), also produced a concentration-dependent decrease in Isc with an EC50 of 0.04+/-0.01 microM; the addition of yohimbine (0.3 microM) increased the EC50 value of UK14,304 to 0.68+/-0.01 microM. The addition of amiloride (100 microM), a Na+ channel blocker, to the fluid bathing the apical side was found not to change the effect of dopamine on Isc. 5-(N-ethyl-N-isopropyl)-amiloride (10 microM), a selective Na+/H+ exchanger inhibitor, partially antagonised the effect produced by 100 microM of dopamine. The addition of ouabain (1 mM) to the fluid bathing the basal side, antagonised the effect produced by 50 and 100 microM of dopamine. In contrast, frusemide (1 mM) completely abolished the effect of all concentrations of dopamine. Forskolin (10 microM) and N6,2'-O-dibutyryl cyclic AMP (1 mM) added to both the apical and serosal sides completely abolished the effect of dopamine on Isc. It is concluded that the dopamine antisecretory effects in the jejunum of adult rats are mediated through alpha2-adrenoceptors. This effect is sensitive to increases in intracellular cyclic AMP and is primarily dependent on the basal Na+,K+,2Cl- -co-transport mechanism.
Vieira-Coelho
M A
MA
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
P
P
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003994:Bucladesine / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004573:Electrolytes / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D004232:Diuretics; D004573:Electrolytes; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D005576:Colforsin; D000068438:Brimonidine Tartrate; D010042:Ouabain; D003994:Bucladesine; D000584:Amiloride; D005665:Furosemide; D011433:Propranolol; D004298:Dopamine; D011224:Prazosin; D010646:Phentolamine