Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

The insulin-like growth factors, insulin-like growth factor I and insulin-like growth factor II are bound to six distinct classes of insulin-like growth factor binding proteins (IGFBPs) in the circulation and in extracellular fluids. Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggestive of a renotropic function for insulin-like growth factor I. In order to examine a possible involvement of IGFBPs in initial diabetic kidney growth and in kidney insulin-like growth factor I accumulation, we studied rat kidney IGFBPs by ligand blotting during the first 4 days after induction of diabetes. Six distinct bands were identified in kidney and liver tissue with apparent molecular weight values of 38-47 (doublet), 34, 30, 24 and 20 kDa. The 38-47 kDa doublet band probably corresponds to the insulin-like growth factor binding subunit of IGFBP-3, the 24 kDa band to IGFBP-4 and the 30 kDa band to IGFBP-1 and/or IGFBP-2, as these IGFBPs in rats have similar molecular weight. In untreated diabetic rats a transient increase in the kidney 30 kDa band was demonstrable 24 h after induction of diabetes with a maximal rise (two-fold) after 48 h, followed by a decrease to baseline values after 4 days. In untreated diabetic rats the 38-47 kDa doublet band also increased (two-fold) in kidney during the first 2 days after induction of diabetes, followed by a subsequent decrease. Insulin-treatment prevented both the increase in the 30 kDa and in the 38-47 kDa bands.(ABSTRACT TRUNCATED AT 250 WORDS)

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/ M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/MGP receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/MGP receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/MGP receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/MGP receptor antiserum (no. 66416) and lz51-protein A or an immunoperoxidase stain. IGF-II/MGP receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/MGP receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing Y-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing Y-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with '251-IGF-II: as with IGF-II/MGP receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs. In conclusion, 1) the IGF-II/MGP receptor is present in multipie human tissues, 2) the human IGF-II/MGP recentor is variablv exnressed in different organs, 3) there is a m&h lesser degree of developmental regulation of IGF-II/ M6P receptor expression in the human than has been reported for the rat or sheep, 4) the differential pattern of distribution of IGF-II/MGP receptor and IGFBPs in the various organs throughout fetal and early postnatal human life points to an important and tissue specific role of the IGF binding principles in development and growth. (J...

In the present study we investigated pharmacological, biochemical, and immunological characteristics as well as the tissue distribution of the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract, and compared the data with those from corresponding experiments for the IGF-I receptor. Competitive binding and affinity cross-linking studies with [125I]IGF-II, and [125I]IGF-I respectively, in rat jejunum yielded results analogous to those previously obtained for IGF-II/M6P and IGF-I receptors in intestinal epithelial membranes and other tissues. Furthermore, the IGF-II/M6P receptor antibody no. 3637 completely inhibited the association of [125I]IGF-II with receptor protein but nonimmune antibody did not, providing additional evidence for the presence of the IGF-II/M6P receptor in the rat gut. Also, analysis of the IGF-II/M6P receptor by immunoblotting using antiserum no. 3637 identified a specific band of mol wt 220.000 throughout the gastrointestinal tract with the highest content of immunoreactivity being present in colon and ileum. Autoradiographic mapping of the distribution of IGF-receptors in the rat gut showed that the expression of IGF-II/M6P receptors was in general 2-3 times greater than that of IGF-I receptors. IGF-II/M6P receptors were found 1) in greatest densities in colon and ileum, 2) more abundantly in the mucosa than in the muscularis propria, and 3) predominantly in the luminal part of the mucosal epithelial cells. Radioimmunocytochemistry employing anti-IGF-II/M6P receptor antibody no. 3637 and [125I]protein A demonstrated an IGF-II/M6P receptor distribution analogous to that shown by autoradiography with [125I]IGF-II). IGF-I receptors were present 1) in greatest densities in ileum and colon, 2) more abundantly in the muscularis propria than in the mucosa, and 3) within the mucosa in greater densities in the lamina propria than in the surface epithelium. For both receptor types densities were greater in crypt than in villous epithelial cells. We conclude: 1) the presence of IGF-II/M6P receptors throughout the rat gastrointestinal tract points to an important role for IGF-II in this organ, 2) the finding of different patterns of distribution for IGF-II/M6P and IGF-I receptors supports the concept of their different principal functions, 3) a high degree of expression of both receptor types in crypt epithelium suggests an essential role for both IGF receptors in the regulation of cell mitogenesis and growth.