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2-AdrenoceptorMediated Modulation of Jejunal Epithelial Transport in Young and Adult Rats1
Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal
2To whom correspondence should be addressed.
This study examined the effect of food deprivation on the jejunal
response to
2-adrenoceptor activation in young
(20-d-old) and adult (60-d-old) rats, using short-circuit
(Isc) measurements in the absence or presence of furosemide
(1 mmol/L). The effect of
2-adrenoceptor stimulation by
5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine
(UK 14,304; 0.33000 nmol/L) was a concentration-dependent
decrease in Isc with similar half-maximal effective
concentration (EC50; 12.3 ± 1.1 vs. 9.6 ± 1.1
nmol/L) and maximal effect (Emax; 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 Isc in fed and
food-deprived rats was markedly (P < 0.05)
attenuated by furosemide (1 mmol/L). Emax 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
EC50 values. The effect of UK 14,304 on Isc 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 [3H]-rauwolscine binding
in membranes from jejunal epithelial cells revealed the presence of a
single class of binding sites, with an apparent
KD in the low nmol/L range. In 20-d-old
food-deprived rats, specific [3H]-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
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
2-adrenoceptors.
KEY WORDS: rat jejunum
2-adrenoceptors Na+,K+,2Cl--co-transporter Na+K+-ATPase