Food Deprivation Increases α2-Adrenoceptor–Mediated Modulation of Jejunal Epithelial Transport in Young and Adult Rats

Abstract

This study examined the effect of food deprivation on the jejunal response to alpha(2)-adrenoceptor activation in young (20-d-old) and adult (60-d-old) rats, using short-circuit (I(sc)) measurements in the absence or presence of furosemide (1 mmol/L). The effect of alpha(2)-adrenoceptor stimulation by 5-bromo-N:-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304; 0.3-3000 nmol/L) was a concentration-dependent decrease in I(sc) with similar half-maximal effective concentration (EC(50); 12.3 +/- 1.1 vs. 9.6 +/- 1.1 nmol/L) and maximal effect (E(max); 70.6 +/- 6.9 vs. 80.6 +/- 4.5% of reduction) values in adult food-deprived and fed rats. The effect of UK 14,304 on I(sc) in fed and food-deprived rats was markedly (P: < 0.05) attenuated by furosemide (1 mmol/L). E(max) values for UK 14,304 in 20-d-old food-deprived rats were higher (P: < 0.05) than those observed in fed rats (93.3 +/- 3.3 vs. 67.0 +/- 11.3% of reduction), without differences in EC(50) values. The effect of UK 14,304 on I(sc) in 20-d-old fed rats was completely abolished by furosemide (1 mmol/L). In food-deprived young rats, the effect of UK 14,304 was also markedly (P: < 0.05) antagonized by furosemide, but not completely abolished. Specific [(3)H]-rauwolscine binding in membranes from jejunal epithelial cells revealed the presence of a single class of binding sites, with an apparent K:(D) in the low nmol/L range. In 20-d-old food-deprived rats, specific [(3)H]-rauwolscine binding was markedly increased, and this was reversed by refeeding. Na(+),K(+)-ATPase activity in isolated jejunal epithelial cells from 60-d-old fed rats was twice that in 20-d-old fed rats [117 +/- 14 vs. 52 +/- 5 nmol free inorganic phosphorus/(mg protein.min)]. Food deprivation in adult rats, but not in 20-d-old rats, was accompanied by a significant decrease in Na(+),K(+)-ATPase activity. In both young and adult rats (fed and food-deprived), UK 14,304 did not affect Na(+),K(+)-ATPase activity. In conclusion, food deprivation in 20-d-old rats enhanced the response to alpha(2)-adrenoceptor stimulation. This effect, which depends primarily on the stimulation of a furosemide-sensitive antisecretory mechanism, is suggested to result from increases in the number of jejunal epithelial alpha(2)-adrenoceptors.