Platelet alpha-adrenergic receptors in obesity: alteration with weight loss.

We studied platelet alpha-adrenergic receptor concentration and function in 19 subjects with simple obesity participating in a double-blind, controlled clinical trial of diet and anorexiants (phentermine, fenfluramine, or a combination of the two) or placebo. From wk 1 to wk 8, weight loss for the group as a whole was 4.9 +/- 0.7 kg (mean +/- SE). Concomitant with this weight loss, the platelet alpha-adrenergic receptor concentration rose from 85.7 +/- 5.8 to 113 +/- 5.8 fmol/mg protein. This increase moved the values for the obese subjects toward or beyond values in lean controls (100 +/- 10.5 fmol/mg protein). The response in the different treatment groups was similar. The receptor concentration increase was accompanied by a corresponding increase in alpha-adrenergic receptor-mediated platelet aggregation. For individual subjects the extent of weight loss over time generally correlated with percent receptor change. Altered adrenergic sensitivity occurring in obese subjects who are losing weight may have important implications in relation to external (therapeutic or inadvertent) administration of catecholamines.

Age-associated differences in guinea pig myocardial Na+, K+-ATPase activity and ouabain inhibition and in Mg2+-ATPase activity.

The influence of age on activity of cardiac Mg2+-ATPase and Na+, K+-ATPase from guinea pigs was studied. Tissue homogenates and NaI-washed membranes were prepared from the heart tissue of 10- to 12-day-old or greater than 12-month-old male guinea pigs. Tissue homogenates from the young animals had significantly greater enzyme activities than those from the older. Na+, K+-ATPase activity in young tissue preparations was less inhibited by ouabain than in older tissue preparations. These differences may be related to the observations that young animals and humans are less sensitive to cardiac glycosides than adults.

Age-associated changes in tissue distribution and uptake of 3H-digoxin in mice and guinea pigs.

The influence of age on tissue distribution of digoxin in mice and guinea pigs and uptake by mouse heart slices was investigated. 4 h after a single dose of 3 H-digoxin, tissue:plasma ratios were significantly greater in very young animals and declined with increasing age. A similar relationship was apparent for packed red blood cell:plasma concentration ratios in mice. Uptake of 3H-digoxin by heart tissue slices was also higher for 21-day-old mice than 200-day-old mice. These data seem to correlate with the larger volume of distribution of digoxin observed in the young. Tissue digoxin relative to plasma concentration seems higher in the young, although they appear less sensitive to the effects of cardiac glycosides.

Reduced variation of tracer binding in digoxin radioimmunoassay by use of (125I)-labeled tyrosine-methyl-ester derivative: relation of thyroxine concentration to binding.

Between-sample variation in tracer binding in the 125I-labeled digoxin radioimmunoassay was investigated with two tracers, 3-O-succinyl-digoxigenin-[125I]-labeled tyrosine and [125I]-labeled tyrosine-methyl-ester-digoxin. Digoxin-free serum samples having various concentrations of thyroxine were assayed with both tracers. The percentage of tracer bound when the samples were assayed with the first-mentioned tracer was increased significantly for the low thyroxine groups when compared to the normal (P less than 0.001) or the high thyroxine groups (P less than 0.05). Little difference existed when the latter tracer was used. There was variation in tracer binding when serum from dogs dosed with thyrotropin was assayed with the first tracer, but there was little variation with the second. Tracer binding may be influenced by thyroxine-binding proteins. Variation in tracer binding appears to be reduced when [125I]-labeled tyrosine-methyl-ester-digoxin is used.