ALPHA(2)-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 receptor s 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 circui t current (mu A/cm(2)) were measured continuously as an index of elect rogenic ion transfer. Dopamine (0.1-100 mu M) produced a concentration dependent decrease in I-sc with an EC50 of 1.4 +/- 0.1 mu M; the effe ct of dopamine was not changed by propranolol (1 mu M), prazosin (1 mu M and 10 mu M) or (+/-)-sulpiride (1 mu M), but was completely abolis hed by phentolamine (1 mu M). The addition of phentolamine (0.3 mu M) or yohimbine (0.3 mu M) produced a rightward shift of the dopamine con centration-dependent curve with an increase in EC50 values up to 30.0 +/- 0.2 mu M and 11.7 +/- 0.1 mu M, respectively. The alpha(2)-adrenoc eptor-selective agonist, UK14,304 (4,5-dihydro-1H-imidazol-2-yl)-6-qui noxalinamine), also produced a concentration-dependent decrease in I-s c with an EC50 of 0.04 +/- 0.01 mu M; the addition of yohimbine (0.3 m u M) increased the EC50 value of UK14,304 to 0.68 +/- 0.01 mu M. The a ddition of amiloride (100 mu M), a Na+ channel blocker, to the fluid b athing the apical side was found not to change the effect of dopamine on 1(sc). 5-(N-ethyl-N-isopropyl)-amiloride (10 mu M), a selective Na/H+ exchanger inhibitor, partially antagonised the effect produced by 100 mu M of dopamine. The addition of ouabain (1 mM) to the fluid bath ing the basal side, antagonised the effect produced by 50 and 100 mu M of dopamine. In contrast, frusemide (1 mM) completely abolished the e ffect of all concentrations of dopamine. Forskolin (10 mu M) and N-6,2 '-O-dibutyryl cyclic AMP (1 mM) added to both the apical and serosal s ides completely abolished the effect of dopamine on I,,. It is conclud ed that the dopamine antisecretory effects in the jejunum of adult rat s are mediated through alpha(2)-adrenoceptors. This effect is sensitiv e to increases in intracellular cyclic AMP and is primarily dependent on the basal Na+,K+,2Cl(-)-co-transport mechanism. (C) 1998 Elsevier S cience B.V. All rights reserved.