Food deprivation increases alpha(2)-adrenoceptor-mediated modulation of jejunal epithelial transport in young and adult rats

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 b y 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 (EC50; 12.3 +/- 1.1 vs. 9.6 +/- 1.1 nm ol/L) and maximal effect (E-max; 70.6 +/- 6.9 vs. 80.6 +/- 4.5% of reductio n) 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 fur osemide (1 mmol/L). E-max values for UK 14,304 in 20-d-old food-deprived ra ts 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 EC50 values. The effe ct of UK 14,304 on I,, in 20-d-old fed rats was completely abolished by fur osemide (1 mmol/L). In food-deprived young rats, the effect of UK 14,304 wa s also markedly (P < 0.05) antagonized by furosemide, but not completely ab olished. Specific [H-3]-rauwolscine binding in membranes from jejunal epith elial 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, sp ecific [H-3]-rauwolscine binding was markedly increased, and this was rever sed by refeeding. Na+,K+-ATPase activity in isolated jejunal epithelial cel ls from 60-d-old fed rats was twice that in 20-d-old fed rats [117 +/- 14 v s. 52 +/- 5 nmol free inorganic phosphorus/(mg protein min)]. Food deprivat ion in adult rats, but not in 20-d-old rats, was accompanied by a significa nt decrease in Na+,K+-ATPase activity. In both young and adult rats (fed an d food-deprived), UK 14,304 did not affect Na+,K+-ATPase activity. In concl usion, food deprivation in 20-d-old rats enhanced the response to alpha(2)- adrenoceptor stimulation. This effect, which depends primarily on the stimu lation of a furosemide-sensitive antisecretory mechanism, is suggested to r esult from increases in the number of jejunal epithelial alpha(2)-adrenocep tors.