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At least 577 records · Page 32Linked to original sources
PubMed1975

Amino acid transport by aggregates of cultured chicken heart cells. Effect of insulin.

Single heart cells dissociated from 14-day-old chicken embryos were reagregated into spheroidal clusters on a gyratory shaker and centrifuged to form cohesive discs of approximately 400 aggregates. These cultured cells accumulated 2-amino[1-14C]isobutyric acid against a gradient. When incubated for 3 hours in a protein-free, buffered, balanced salt solution, concentrative transport decreased to a stable basal level. Incubation in the presence of sodium bovine insulin prevented this fall in transport activity and resulted in increased 2-aminoisobutyric acid uptake to concentrations 40 time sthat in the medium during a subsequent 3-hour transport assay. Intracellular accumulation of 2-aminoisobutyric acid was linear during the initial 15 min of transport in the presence and absence of added insulin. Basal transport of 2-aminoisobutyric acid was temperature-dependent, requied extracellular sodium greater than 125 meg/liter, and demonstrated saturation with an apparent Vmax of 3.4 mmol/liter/10 min and an apparent Km of 2.6 mM. Basal transport activity was not reduced by cycloheximide or puromycin even after 3 hours of exposure...

Aminoisobutyric Acids↗
PubMed1976

[Amino acid transport by membrane vesicles of virally transformed and nontransformed cells: effects of sodium gradient and cell density].

Mixed membrane vesicle populations composed of plasma membrane and endoplasmic reticulum were prepared from Balb/c 3T3 and simian virus 40-transformed Balb/c 3T3 mouse fibroblasts. The initial rates of uptake of L-leucine and alpha-aminoisobutyric acid by these vesicles were stimulated by a NaCl gradient (external greater than internal). Cation specificity for stimulation of L-leucine uptake was Na+ greater than Li+ greater than K+. NaSCN was as effective as NaCl. Stimulation of uptake of both amino acids by a NaCl gradient was twice as great in vesicles from transformed as compared to non-transformed cells. The NaCl gradient produced transient accumulation of both L-leucine and alpha-aminoisobutyric acid to twice the equilibrium level in vesicles from transformed cells. No such "overshoot" was observed in vesicles from nontransformed cells. In vesicles from the contact-inhibitable Balb/c 3T3 cells, transport of alpha-aminoisobutyric acid, but non L-leucine, exhibited a density-dependent decrease in Na+ gradient induced stimulation, from 248% for sub-confluent to 109% with confluent cells. No density-related changes in uptake were noted with vesicles from the transformed cells. These studies suggest that variation in amino acid uptake associated with viral transformation may be related, at least in part, to alterations in Na+ permeability of the surface membrane.

Aminoisobutyric Acids↗
PubMed1979

The effect of fluoride on the cellular uptake and pool of amino acids.

Fluoride decreased the initial uptake of 2-aminoisobutyric acid (AIB) in LS cells only in high (supralethal) concentrations and after several hours of exposure. The steady state level of AIB seemed somewhat more sensitive as it was halved after 23 hours exposure to 6 mM-NaF. The cellular levels of some natural amino acids were also reduced by fluoride. However, cells resistant to fluoride showed equally lowered levels of amino acids, indicating that the observed effect of fluoride on cellular amino acid levels may be of little importance.

Amino Acids↗
PubMed1977

High turnover rate of transfer RNA in tumor tissue.

Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g., N2,N2-dimethylguanosine, can originate only from transfer RNA (tRNA). Until recently, it could not be ascertained whether the high level of excretion of such compounds is due to cell death or specific tRNA turnover. However, an approach to this problem became feasible, with beta-aminoisobutyric acid as a probe. This compound is a terminal degradation product of thymine which is present in both DNA and tRNA. Since the pathway of synthesis of thymine is different in the two macromolecules, it and its end product, beta-aminoisobutyric acid can be differentially labeled with [14C]formate and [3H3]methylmethionine as precursors. Therefore the ratio of the two labels in the excreted beta-aminoisobutyric acid is a measure of the macromolecular origin of the degradation product. We have found from such analysis that tRNA's are not homogeneous in their turnover rate. There is a subpopulation that turns over much faster than the rest. The turnover rate of a subpopulation of tRNA's in tumor tissue exceeds the turnover rate of tRNA's in normal tissue. Such rapid degradation of tRNA's must be the source of the massive excretion of modified nucleosides by cancer patients which can be 10-fold higher than in normal subjects.

Aminoisobutyric Acids↗
PubMed1985

Amino acid transport by corneal epithelial cells from the toad, Bufo marinus.

alpha-Aminoisobutyric acid is actively accumulated by the epithelium of the cornea of the toad, Bufo marinus, resulting in a tissue to medium ratio of 4 to 1 after 40 min of incubation. The accumulation of alpha-aminoisobutyric acid is ouabain-sensitive and dependent upon the presence of extracellular sodium. Transport is inhibited by carbon monoxide, 6-aminonicotinamide, arsenite and n-heptyl-3-hydroxy-quinoline-n-oxide and stimulated by diamide.

Aminoisobutyric Acids↗
PubMed1989

The Proton Electrochemical Transmembrane Gradients Generated by the Transfer Cells of the Haustorium of Polytrichum formosum and Their Use in the Uptake of Amino Acids.

The epidermal cells of the sporophyte haustorium of Polytrichum formosum are modified into transfer cells. These cells are located in a strategic place allowing them to control the exchanges between the two generations. Their plasmalemma creates proton gradients (Deltapsi and DeltapH) which increase during the development of the sporophyte. As the sporophyte grows from 2 to 4 cm long, the pH of the incubation medium of the haustoria decreases from 5.2 to 4.3, and the transmembrane potential difference (PD) hyperpolarizes form -140 to -210 millivolts. These gradients become rapidly larger than that generated by the plasmalemma of the basal cells of the sporophyte. They are used to energize the uptake of the solutes present in the apoplast of the gametophyte, particularly the amino acids. Below 20 micromolar alpha-aminoisobutyric acid uptake in the transfer cells is mediated by a saturable system and is optimal at acidic pH (4.0 and 4.5). It is strongly inhibited by compounds dissipating both Deltapsi and DeltapH (10 micromolar carbonylcyanide-m-chlorophenyl hydrazone) or only Deltapsi (0.1 molar KCl). The absorption of alpha-aminoisobutyric acid and of the other neutral amino acids tested induces an alkalinization of the medium and a depolarization of membrane potential difference which is concentration dependent. These data show that the uptake of amino acids by the transfer cells of the haustorium is a secondary translocation (proton-amino acid symport) energized by a primary translocation (proton efflux). More particularly, they show that transfer cells possess a membrane enzymic equipment particularly efficient to achieve the uptake of the solutes leaked in the apoplast from other cell types.

Journal Article↗
PubMed1988

Clarification of signaling pathways mediated by insulin and insulin-like growth factor I receptors in fibroblasts from patients with specific defect in insulin receptor.

Receptor binding and biological action of insulin and insulin-like growth factor I (IGF-I) were studied in fibroblasts from a patient with leprechaunism and a patient with type A syndrome of insulin resistance. Insulin binding was reduced to 18.8 and 27.7% of control value, respectively. In contrast, IGF-I binding was normal in both patients. In competitive binding studies, IGF-I had 0.2% of the ability of insulin to compete with 125I-labeled insulin binding, and insulin had 0.1% of the ability of IGF-I to compete with 125I-labeled IGF-I binding in control subjects and patient fibroblasts. The dose-response curves of insulin stimulation assessed by glucose incorporation and alpha-aminoisobutyric acid uptake showed normal responsiveness, and ED50 was significantly shifted to the right in fibroblasts from both patients. However, normal responsiveness and sensitivity were observed in thymidine incorporation studies. For IGF-I, dose-response curves of glucose incorporation, alpha-aminoisobutyric acid uptake, and thymidine incorporation were all normal in both patients. These results indicate that 1) the defect is specific to the insulin-receptor binding in these patients, 2) insulin and IGF-I activate glucose incorporation and alpha-aminoisobutyric acid uptake mainly through their own specific receptors, but 3) the IGF-I receptor appears to have a more important role in stimulating thymidine incorporation than the insulin receptor in physiological condition or, alternatively, an unknown postreceptor process with cascade signal transmission may overcome the decreased insulin-receptor binding to produce a normal dose-response curve.

Aminoisobutyric Acids↗
PubMed1980

Different levels of changes induced by the insecticide lindane in cultured C-6 glioma cells.

The effects of lindane on alpha-aminoisobutyric acid and uridine uptake were studied in the rat line C-6 of glial origin. Different levels of modifications could be distinguished by use of 2 modes of investigation. One study, carried out within minutes of contact with lindane, has shown that the inhibition of alpha-aminoisobutyric acid and uridine uptake was rapid and immediately reversible. The other study, carried out after several hours of treatment followed by a 15-min triple washing, has allowed to attribute the non-reversible decrease in uridine uptake induced by a 20-h treatment to an inhibition of protein synthesis, and the increase in alpha-aminoisobutyric acid uptake to the derepression of synthesis of transport proteins.

Aminoisobutyric Acids↗
PubMed1987

The effect of hyperosmotic blood-brain barrier disruption on blood-to-tissue transport in ENU-induced gliomas.

Hyperosmotic blood-brain barrier disruption transiently increases the rate of blood-to-tissue transport of water-soluble compounds to normal brain and has been used in brain tumor patients to increase the delivery of chemotherapeutic drugs. This method remains controversial; debate concerns the extent to which it increases drug delivery to brain tumors. Ethylnitrosourea (ENU)-induced gliomas in rats have the lowest rate of blood-to-tissue transfer of the water-soluble compound alpha-aminoisobutyric acid of all experimental brain tumors studied to date. To gain further understanding about the effects of hyperosmotic blood-brain barrier disruption in brain tumors, we measured the unidirectional blood-to-tissue transfer constant of alpha-aminoisobutyric acid in ENU-induced brain tumors in rats after hyperosmotic disruption. Hyperosmotic blood-brain barrier disruption with 1.6 osmolar mannitol resulted in an averaged whole-tumor transfer constant of 0.013 +/- 0.003 (standard error) mL/(g/min), compared to a transfer constant of 0.007 +/- 0.002 mL/(g/min) for ENU-induced gliomas in the contralateral undisrupted hemisphere, a difference that was not significant. In contrast, hyperosmotic blood-brain barrier disruption produced a large and significant increase in the transfer constant of alpha-aminoisobutyric acid in tumor-free cortex (from 0.002 +/- 0.001 to 0.05 +/- 0.011 mL/[g/min]) and in tumor-free corpus callosum (from 0.001 +/- 0.003 to 0.017 +/- 0.005 mL/[g/min]). Hyperosmotic blood-brain barrier disruption does not appear to be an efficient method with which to increase the rate of delivery of water-soluble drugs to brain tumors but does result in a significant increase in the delivery rate of these drugs to normal brain tissue.

Aminoisobutyric Acids↗
PubMed2004

beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities.

beta-Ureidopropionase deficiency is an inborn error of the pyrimidine degradation pathway, affecting the cleavage of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid. In this study, we report the elucidation of the genetic basis underlying a beta-ureidopropionase deficiency in four patients presenting with neurological abnormalities and strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine. No beta-ureidopropionase activity could be detected in a liver biopsy obtained from one of the patients, which reflected the complete absence of the beta-ureidopropionase protein. Analysis of the beta-ureidopropionase gene (UPB1) of these patients revealed the presence of two splice-site mutations (IVS1-2A>G and IVS8-1G>A) and one missense mutation (A85E). Heterologous expression of the mutant enzyme in Escherichia coli showed that the A85E mutation resulted in a mutant beta-ureidopropionase enzyme without residual activity. Our results demonstrate that the N-carbamyl-beta-amino aciduria in these patients is due to a deficiency of beta-ureidopropionase, which is caused by mutations in the UPB1 gene. Furthermore, an altered homeostasis of beta-aminoisobutyric acid and/or increased oxidative stress might contribute to some of the clinical abnormalities encountered in patients with a beta-ureidopropionase deficiency. An analysis of the presence of the two splice site mutations and the missense mutation in 95 controls identified one individual who proved to be heterozygous for the IVS8-1G>A mutation. Thus, a beta-ureidopropionase deficiency might not be as rare as is generally considered.

Amidohydrolases↗
PubMed1984

Autoregulation by iodine of thyroid protein synthesis: influence of iodine on amino acid transport in cultured thyroid cells.

Studies were conducted to determine whether the inhibitory effect of iodine on thyroid protein synthesis could be explained by a reduction in intracellular amino acid transport. The nonmetabolizable amino acid [14C]cycloleucine was used as a probe for the L system of neutral amino acid transport in dog thyroid cells during the initial 24 h of primary culture. Uptake of cycloleucine was linear for up to 30 min. At all time points, cycloleucine transport was reduced in cells preincubated for 3 h in NaI (10(-4) M). Inhibition (in a typical experiment) by NaI of cycloleucine transport (10 min) was 19%, 42%, and 69% at 10(-6), 10(-5), and 10(-4) M iodide, respectively. Methimazole (3 mM) together with iodide abolished the inhibitory effect of iodide on cycloleucine transport, implying the necessity of iodide organification. Methimazole itself did not significantly alter cycloleucine transport. T3, T4, MIT, and DIT similarly did not inhibit cycloleucine transport. NaI did not inhibit cycloleucine transport in cells lacking a mechanism for iodide organification. Double reciprocal plots of cycloleucine influx at different substrate concentrations indicated that NaI decreases the maximum velocity of cycloleucine transport (2.1 vs. 4.0 nmol min-1 mg protein-1) without affecting the Km (1 mM). In contrast to influx, iodine did not affect cycloleucine efflux. The inhibitory action of iodine on cycloleucine transport was reversible after removal of extracellular iodide, with full recovery occurring within 24 h. Iodine similarly inhibited the cellular uptake of [14C] alpha-methylaminoisobutyric acid as well as [14C] alpha-aminoisobutyric acid in the presence of 30 mM methyl-alpha-aminoisobutyric acid, that is of specific probes for the A and ASC transport systems of neutral amino acids, respectively. These data indicate that autoregulation by iodine of thyroid protein synthesis occurs, at least in part, by regulation of the maximum velocity of neutral amino acid uptake via the A, ASC, and L transport systems.

Amino Acids↗
PubMedDate not supplied

Ethanol-induced intrauterine growth retardation: correlation with placental glucose transfer.

Placental transfer of glucose and alanine analogs was studied at term in ethanol-fed and control rats. Ethanol was provided as 30% of the caloric intake throughout gestation. Control groups received isocaloric liquid diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of pregnancy, the rats were injected with a mixture of [3H]2-deoxyglucose and [14C]alpha-aminoisobutyric acid. The ratios of fetal:maternal plasma radioactivities 1 hr later were used to compare placental transfer between the groups. Mean +/- SE body weight of EF fetuses (4.54 +/- 0.07 g) was significantly lower than that of PF (4.88 +/- 0.06 g) or AF (5.17 +/- 0.09 g) fetuses. Maternal ethanol ingestion reduced placental transfer of 2-deoxyglucose and alpha-aminoisobutyric acid by 12% and 35%, respectively. Placental transfer of both analogs was not affected in the PF controls. The weight of EF fetuses correlated (p less than 0.001) with transfer of 2-deoxyglucose to the fetus. This relationship was also found in the control groups. Fetal body weight did not show a strong correlation with alpha-aminoisobutyric acid transfer. Thus, impaired transfer of glucose to the fetus may play a significant role in the growth retardation observed in fetuses of ethanol-fed rats.

Alanine↗
PubMed1987

Simultaneous measurements of blood flow and blood-to-tissue transport in xenotransplanted medulloblastomas.

We used double-label quantitative autoradiography to study blood flow (with [131I]iodoantipyrine) and blood-to-tissue transport (with [14C]-alpha-aminoisobutyric acid) in 20 TE-671 medulloblastomas xenotransplanted into nude rats. Microscopically, two distinct patterns of tumor growth were observed: (a) a solid tumor mass; and (b) a tumor in which nearly all tumor cells were located perivascularly. These two tumor patterns differed markedly in values of blood flow (F) and the transfer constant (K) of alpha-aminoisobutyric acid. The solid tumors (N = 17) had averaged mean values of F = 36.8 +/- 5.3 (SE) and K = 8.0 +/- 0.7 ml/100 g/min. The perivascular tumors, which were fewer in number (N = 3), had averaged mean values of F = 83.8 +/- 9.8 and K = 0.4 +/- 0.06 ml/100 g/min. Calculated values of the net extraction fraction (En) of alpha-aminoisobutyric acid were 0.54 +/- 0.07 for the solid tumors and 0.009 +/- 0.001 for the perivascular tumors. K and En for the solid tumors are the highest for any brain tumor model reported to date. The high rates of blood-to-tissue transport may explain why intracranial TE-671 medulloblastomas in nude mice respond to treatment with water-soluble chemotherapeutic drugs, unlike most other brain tumor models.

Aminoisobutyric Acids↗
PubMed1984

Peptide sweeteners. 6. Structural studies on the C-terminal amino acid of L-aspartyl dipeptide sweeteners.

Stereochemical and structural aspects of the variations in the C-terminal residue of L-aspartyl-L-phenylalanine methyl ester have been investigated. Novel configurational analogues such as L-aspartyl-D-alanine benzyl ester and L-aspartyl-D-alpha-aminobutyric acid benzyl ester were found to be sweet. In addition, chiral and achiral alpha, alpha-dialkylglycine and alpha-aminocycloalkanecarboxylic acids were incorporated into the dipeptides. The L-aspartic acid based dipeptide derivatives of alpha-aminoisobutyric acid methyl ester, alpha-aminocyclopropanecarboxylic acid methyl ester, alpha-aminocyclobutanecarboxylic acid methyl ester, and alpha-aminocyclopentanecarboxylic acid methyl ester are sweet. Dipeptides with alpha-aminocyclohexanecarboxylic acid methyl ester and alpha-aminocycloheptanecarboxylic acid methyl ester are bitter, whereas the analogues with alpha-aminocyclooctanecarboxylic acid methyl ester, alpha, alpha-diethylglycine methyl ester, and alpha-aminoisobutyric acid benzyl ester are tasteless. Aspects on chirality and effective volume of the C-terminal residue are discussed and correlated with taste.

Aspartame↗
PubMed1995

Chloride-dependent amino acid transport in the small intestine: occurrence and significance.

The unidirectional influx of amino acids, D-glucose and ions across the brush-border membrane of the small intestine of different species has been measured in vitro with emphasis on characterization of topographic and species differences and on chloride dependence. The regional differences in transport along the small intestine are outlined and shown to be caused by variation in transport capacity, while the apparent affinity constants are unchanged. Rabbit small intestine is unique by exhibiting maximal rates of transport in the distal ileum and a very steep decline in the oral direction from where tissues are normally harvested for preparation of brush-border membrane vesicles. Transport in the guinea pig and rat is much more constant throughout the small intestine. Since the capacity of nutrient carriers is regulated by their substrates it is possible that bacterial breakdown of peptides and proteins in rabbit distal ileum increases the concentration of amino acids leading to an upregulation of the carriers. Chloride dependence is a characteristics of the carrier rather than the transported amino acid, and is used to improve the classification of amino acid carriers in rabbit small intestine. In this species the imino acid carrier, the beta-amino acid carrier, and the beta-alanine carrier, which should be renamed the B0,+ carrier, are chloride-dependent. The steady-state mucosal uptake of classical substrates for these carriers in biopsies from the human duodenum is also chloride-dependent. The carrier of beta-amino acids emerges as ubiquitous and chloride-dependent, and evidence of cotransport with both sodium and chloride is reviewed. A sodium:chloride:2-methyl-aminoisobutyric acid coupling stoichiometry of approx. 2:1:1 is suggested by ion activation studies. Direct measurements of coupled ion fluxes in rabbit distal ileum confirm that sodium, chloride and 2-methyl-aminoisobutyric acid are cotransported on the imino acid carrier with an identical influx stoichiometry. Control experiments and reference to the literature on the electrophysiology of the small intestine exclude alterations of the membrane potential as a feasible explanation of the chloride dependence. Thus, it is concluded that chloride is cotransported with both sodium and 2-methyl-aminoisobutyric acid across the brush-border membrane of rabbit distal ileum.

Amino Acids↗
PubMed1981

Amino acid influx across the mucosal border of the rat intestine in vivo.

The lack of an in vivo method for measuring influx of amino acid into the mucosa has prevented a systematic comparison of characteristics of amino acid influx in vivo with prior in vitro studies. We developed and validated a technique for measuring amino acid influx in vivo. The mucosa is exposed briefly to labelled amino acid perfused luminally at a rapid rate and tissue uptake is measured. The brief exposure period insures that amino acid is confined to the segment. The rapid perfusion rate minimizes concentration of endogenous Na+ in the lumen and permits Na-dependency for alpha-aminoisobutyric acid influx to be demonstrated in vivo for the first time. We also demonstrated the inhibitory effect of K+ and competition by glycine on alpha-aminoisobutyric acid influx in vivo. The saturation kinetics for L-leucine in vivo and in vitro were compared under varying perfusion rates and with and without stirring with air. Under optimal conditions of agitation (rapid perfusion and bubbling with air), the apparent Michaelis constant (Kt) is decreased to be almost equal to that determined under comparable influx conditions in vitro. These studies demonstrate no major difference between characteristics of amino acid transport under more physiologic in vivo conditions as compared with prior in vitro studies.

Amino Acids↗
PubMed1993

Middle cerebral artery occlusion increases cerebral capillary permeability.

One hour after middle cerebral artery occlusion, the regional blood to brain transfer coefficient of alpha-aminoisobutyric acid was determined in eight barbiturate anaesthetized rats. The transfer coefficient (microliter/min-1/g-1) was significantly higher in the ischaemic cortex (10.6 +/- 2.3) than in the contralateral cortex (6.5 +/- 1.0). Cerebral regional capillary surface area was determined in another group of twelve rats using an alkaline phosphatase stain for the total capillary bed and fluorescein isothiocyanate-dextran to visualize the perfused capillaries. Perfused capillary surface area (cm2/cm3) was lower in the ischaemic cortex (141 +/- 31) than in the contralateral cortex (426 +/- 32). Using these values for the transfer coefficient, surface area and our previously published data of regional cerebral blood flow after middle cerebral artery occlusion, we calculated the extraction fraction of alpha-aminoisobutyric acid, the permeability-surface area product and the permeability of cerebral regional capillary beds. Although, there are numerous reports of permeability-surface area product of brain capillaries, to our knowledge, the permeability has never been determined before. The calculated extraction fraction ratio for alpha-aminoisobutyric acid for ischaemic cortex/contralateral cortex was 3.1. Similar ratios for permeability-surface area product and capillary permeability were 1.6 and 4.4, respectively. Thus, there was a more than four fold increase in capillary permeability to small molecules in the ischaemic cortex one hour after middle cerebral artery occlusion.

Aminoisobutyric Acids↗
PubMed1992

Potentiation of insulin-like growth factor (IGF) action by IGF-binding protein-3: studies of underlying mechanism.

In this study we investigated the mechanism(s) by which insulin-like growth factor-binding protein-3 (IGFBP-3) potentiates IGF-I action in cultured bovine fibroblasts. Preincubation of cells with glycosylated or nonglycosylated recombinant human IGFBP-3 enhanced responsiveness to IGF-I in a time-dependent manner. A preincubation period of at least 24 h with IGFBP-3 was required to see a significant effect. Pretreatment with IGFBP-3 for 72 h resulted in a 2- to 4-fold augmentation of IGF-I-stimulated [3H]aminoisobutyric acid uptake; IGFBP-3 had no effect on basal [3H]aminoisobutyric acid uptake. During the preincubation period, exogenous IGFBP-3 associated with the fibroblast surface and exhibited time-dependent processing to lower mol wt forms that retained the ability to bind radiolabeled IGF-I. Initial surface adherence (preincubation time of 24 h or less) was readily reversible. However, IGFBP-3, once processed, appeared to be closely associated with the cell. After 72 h of exposure to bovine fibroblasts, cell-associated IGFBP-3 had a 10-fold lower affinity for IGF-I compared to intact IGFBP-3 in solution. In addition, incubation of bovine fibroblasts with IGFBP-3 had modifying effects on type I IGF receptor-mediated signalling because 1) the bioeffectiveness of [Gln3,Ala4,Tyr15,Leu16]IGF-I and insulin, IGF-I receptor activators with little or no affinity for IGFBP-3, was potentiated by preincubation with IGFBP-3; and 2) fibroblast responsiveness to IGF-I analogs with different affinities for the type I IGF receptor was enhanced in direct relation to the ability of the peptide to bind to the receptor. There was no evidence for an increase in receptor number or affinity as a result of IGFBP-3 treatment. These data suggest that IGFBP-3 potentiation of IGF-I action in bovine fibroblasts may involve changes in IGFBP-3 and type I IGF receptor responsiveness. Thus, cell-associated IGFBP-3 may provide a mechanism for optimal presentation of IGF-I to its receptor as well as a means to heighten receptor reactivity to IGF-I and related peptides.

Aminoisobutyric Acids↗