Intestinal dopaminergic activity in obese and lean Zucker rats: response to high salt intake.

The present study examined intestinal dopaminergic activity and its response to high salt (HS, 1% NaCl over a period of 24 hours) intake in obese (OZR) and lean Zucker rats (LZR). The basal Na+,K+-ATPase activity (nmol Pi/mg protein/min) in the jejunum of OZR was higher than in LZR on normal salt (NS) (OZR-NS = 111.3 +/- 6.0 vs. LZR-NS = 88.0 +/- 8.3). With the increase in salt intake, the basal Na+,K+-ATPase activity significantly increased in both animals (OZR-HS = 145.9 +/- 11.8; LZR-HS = 108.8 +/- 6.7). SKF 38393 (10 nM), a specific D1-like dopamine receptor agonist, inhibited the jejunal Na+,K+-ATPase activity in OZR on HS intake, but failed to inhibit enzyme activity in OZR on NS intake and LZR on NS and HS intakes. The aromatic L-amino acid decarboxylase (AADC) activity in OZR was lower than in LZR on NS intake. The HS intake increased AADC activity in OZR, but not in LZR. During the NS intake the jejunal monoamine oxidase (MAO) activity in OZR was similar to that in LZR. The HS intake significantly decreased MAO activity in both OZR and LZR. The jejunal COMT activity in OZR was higher than in LZR on NS intake. The HS intake reduced COMT activity in OZR but not LZR. It is concluded that inhibition of jejunal Na+,K+-ATPase activity through D1 dopamine receptors is dependent on salt intake in OZR, whereas in LZR, the enzyme failed to respond to the activation of D1 dopamine receptors irrespective of their salt intake.

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 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.

Salt intake and sensitivity of intestinal and renal Na+-K+ atpase to inhibition by dopamine in spontaneous hypertensive and Wistar-Kyoto rats.

The present study evaluated the activity of jejunal Na+-K+-ATPase and its sensitivity to inhibition by dopamine in spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during low (LS), normal (NS) and high (HS) salt intake. Basal jejunal Na+-K+-ATPase activity in SHR on LS intake was higher than in WKY rats. Jejunal Na+-K+-ATPase activity in WKY rats, but not in SHR, on LS intake was significantly reduced (20% decrease) by dopamine (1 microM) and SKF 38393 (10 nM), but not quinerolane (10 nM), this being antagonized the D1 receptor antagonist (SKF 83566). Changing from LS to NS or HS intake in WKY rats increased basal jejunal Na+-K+-ATPase activity and attenuated the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake increased basal jejunal Na+-K+-ATPase activity. Basal renal Na+-K+-ATPase activity in SHR on LS intake was similar to that in WKY rats and was insensitive to inhibition by dopamine. Changing from LS to NS or HS intake in WKY rats increased basal renal Na+-K+-ATPase activity without affecting the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake failed to alter basal renal Na+-K+-ATPase activity. It is concluded that inhibition of jejunal Na+-K+ ATPase activity by D1 dopamine receptor activation is dependent on salt intake in WKY rats, and SHR animals fail to respond to dopamine, irrespective of their salt intake.

Response of jejunal Na+, K+-ATPase to 5-hydroxytryptamine in young and adult rats: effect of fasting and refeeding.

The present study is aimed to evaluate the effects of 5-hydroxytryptamine (5-HT) upon jejunal Na+,K+-ATPase in young (20-day-old) and adult (60-day-old) rats, and determine the effect of food intake on the response of the sodium pump to the amine. Basal Na+,K+-ATPase activity in jejunal epithelial cells from young rats was twice that in adult animals and responded to 5-HT with stimulation. In adult rats, fasting reduced by 25% basal jejunal Na+, K+-ATPase activity, whereas in young rats, no such change was observed. The sensitivity of jejunal Na+,K+-ATPase to 5-HT in young fasted rats was similar to that observed in fed animals. The effect of refeeding in young rats was a 2-fold increase in jejunal Na+, K+-ATPase activity, this being accompanied by insensitivity to 5-HT. In adult rats, refeeding was accompanied by an increase in jejunal Na+,K+-ATPase activity. It is concluded that the stimulatory effect of 5-HT upon jejunal Na+,K+-ATPase activity is a phenomenon dependent on both age and type of diet. In young rats, it is the food intake that plays an important role in development of insensitivity of Na+,K+-ATPase to stimulation by 5-HT, while in adult animals fasting or fasting followed by refeeding does not play a major role in regulating its sensitivity to the amine.

Food intake abolishes the response of rat jejunal Na(+),K(+)-ATPase to dopamine.

The aim of the present study was to evaluate whether the sensitivity of jejunal Na(+),K(+)-ATPase to inhibition by dopamine (DA) in young rats is related to the type of food (breast milk vs. solid) or reflects a developmental adaptation. When 18-d-old rats were separated from their dams and fed solid food (the same used to feed adult rats) for 2 d, intestinal Na(+),K(+)-ATPase activity was significantly greater than that of breast-fed pups of the same age (20 d) (127 +/- 8 vs. 52 +/- 4 nmol Pi. mg protein(-1). min(-1); P < 0.05). Activity in rats fed solid food was insensitive to inhibition by 1 micromol/L DA. Na(+),K(+)-ATPase activity in 60-d-old rats (117. 4 +/- 4.2 nmol Pi. mg protein(-1). min(-1)) was also higher (P < 0. 05) than in breast-fed rats, and DA (1 micromol/L) did not inhibit enzyme activity. The B(max) value for binding of [(3)H]-Sch 23390 in 20-d-old breast-fed rats did not differ from that in age-matched rats fed a solid food for 2 d and or that in 60-d-old rats. Levels of DA, but not L-3,4-dihydroxyphenylalanine and amine metabolites, in the jejunal mucosa of 20-d-old rats that had eaten solid food for 2 d were 60% lower than in age-matched rats, breast-fed rats, and not different from those in the jejunal mucosa of 60-d-old rats fed the solid food. We conclude that in adult rats, in contrast to in young rats, DA does not inhibit jejunal Na(+),K(+)-ATPase activity, and food intake in young rats plays an important role in the development of the insensitivity of Na(+),K(+)-ATPase activity to DA.

Effect of salt intake on jejunal dopamine, Na+,K+-ATPase activity and electrolyte transport.

The present study addresses the question of the relevance of salt intake on jejunal dopamine, Na+,K+-ATPase activity and electrolyte transport. Low salt, but not high salt, intake for 2 weeks increased dopamine levels in the jejunal mucosa accompanied by a marked decrease in L-3,4-dihydroxyphenylalanine tissue levels. By contrast, in rats fasted for 72 h the effect of refeeding for 24 h with a low salt diet failed to change dopamine tissue levels, although it significantly increased those of L-3,4-dihydroxyphenylalanine. By contrast, high salt intake markedly increased the tissue levels of both dopamine and L-3,4-dihydroxyphenylalanine, without changes in dopamine/L-3,4-dihydroxyphenylalanine tissue ratios. Tissue levels of both L-3,4-dihydroxyphenylalanine and dopamine in control conditions (normal salt intake for 2 weeks) were markedly higher (P < 0.05) than in rats submitted to 72 h fasting plus 24 h refeeding. The effect of fasting for 72 h followed by 24 h refeeding was a marked decrease in jejunal Na+,K+-ATPase activity, particularly evident for rats fed a normal salt and high salt diets during the refeeding period. Basal short circuit current was similar in rats fed a normal salt diet for 2 weeks and 24 h, and the type of diet failed to alter basal short circuit current after refeeding with normal, low and high salt diets. On the other hand, the effect of prolonged low salt intake was a marked decrease in jejunal Na+, K+-ATPase activity and basal short circuit current, whereas high salt intake failed to alter enzyme activity and basal short circuit current. In rats fed for 2 weeks a high salt diet ouabain was found to be more potent in reducing jejunal short circuit current than in rats fed normal and low salt diets. The effect of furosemide was more marked in rats fed for 2 weeks high and low salt diets than in animals receiving a normal salt intake. Dopamine (up to 1 micromol L-1) was found not to alter Na+,K+-ATPase and basal short circuit current in jejunal epithelial sheets, in rats fed with normal, low and high salt diets for 2 weeks and 24 h.