Various Tissues Of Rat Research Articles

Albumin clearance in the endotoxemic rat after administration of Nω-nitro-L-arginine methyl ester (L-name)

Endotoxin (LPS) is a powerful activator of the inducible nitric oxide (NO) synthase. Whereas NO seems to be one factor behind the decreased responsiveness of the circulation to adrenergic stimulation in septic shock, the role of NO in increased vascular permeability is less clear. In a former study [1] we have shown that although NO production increased after LPS there was no increased extravasation of albumin in a wide variety of rat tissues examined; on the contrary clearance was decreased in the entire gastrointestinal tract. In this study tissue extravasation was examined after administration of the nitric oxide synthase inhibitor L-NAME.

Characterisation of β 2-adrenoceptors, using the agonist [ [formula omitted]]formoterol and positron emission tomography

The agonist radioligand N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4- [ 11 C] -methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide ( [ 11 C] formoterol) was synthesised in order to test its ability to visualise pulmonary β 2-adrenoceptors in vivo, with positron emission tomography (PET). Formoterol was labelled via reaction of a dibenzyl-protected precursor with [ 11 C] CH 3I. Subsequent deprotection with Pd/C and H 2 yielded [ 11 C] formoterol in 5–15% (corrected for decay) and the specific activity ranged from 5.5–22.2 TBq mmol −1 (150–600 Ci mmol −1), 60–70 min after end of bombardment. Biodistribution studies with [ 11 C] formoterol were performed in male Wistar rats which were either untreated or predosed with ( d, l)-propranolol hydrochloride (2.5 mg kg −1, β-adrenoceptor antagonist), erythro- dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydrochloride (ICI 118551, 0.15 mg kg −1, β 2-adrenoceptor antagonist), isoprenaline (15 mg kg −1, non-subtype selective β-adrenoceptor agonist) or (±)-(2-hydroxy-5-[2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1 H-imidazol-2-yl-)phenoxy)propyl)amino)ethoxy]benzamide)monomethane sulfonate (CGP 20712A, 0.15 mg kg −1, β 1-adrenoceptor antagonist). Lungs, heart, liver and plasma were analysed for radioactive metabolites. The kinetics of [ 11 C] formoterol in the lungs of male Wistar rats were investigated by means of a dynamic PET study. The biodistribution studies showed significant specific binding in tissues known to contain β 2-adrenoceptors (lungs, spleen, and heart). Binding in these organs was blocked by ICI 118551 and isoprenaline, but not by CGP 20712A. [ 11 C] Formoterol was rapidly metabolised in rats but lungs and heart did not substantially take up the labelled metabolites. The binding of [ 11 C] formoterol in various tissues of rats is consistent with the β 2-selectivity of formoterol. Whether [ 11 C] formoterol selectively binds to the high affinity state of β 2-adrenoceptors remains to be elucidated. [ 11 C] Formoterol is potentially useful for studying β 2-adrenoceptors with PET and this radioligand may provide new insights in the mechanisms underlying prolonged sympathomimetic action.

Identification of kinesin-like molecules in myogenic cells

Numerous organelles are repositioned during myogenic differentiation and are maintained in an asymmetric distribution throughout the life span of a myotube. It is likely that members of the kinesin superfamily may be responsible for some or all of these microtubule-dependent movements. Consequently, we have attempted to identify kinesin-like molecules expressed throughout myogenesis. Using a standard PCR-based strategy, we cloned two kinesin-like molecules from a rat myogenic cell line, L6. Sequence analysis of the first of these, KIF3C, defines it as a novel member of the KIF3 subfamily of kinesin-like proteins. KIF3C is expressed throughout myogenesis as well as in numerous rat tissues. Like other members of the KIF3 subfamily, KIF3C has an N-terminal motor domain. The second molecule identified is a rat homolog of murine KIF1B, a putative mitochondrial transporter. KIF1B is also expressed ubiquitously both in myogenic cells at all stages and in a variety of rat tissues.

Localization of a Novel Growth Hormone Releasing Hormone (GHRH) Precursor C-Terminal Peptide Product, GHRH-Related Peptide, in the Rat Ovary. † 414

The gene which encodes growth hormone releasing hormone (GHRH) arose from an ancestral gene that also gave rise to the genes for vasoactive intestinal peptide (VIP), pituitary adenylyl-cyclase activating polypeptide (PACAP), glucagon, and secretin. Review of the GHRH gene sequence predicts a second 30 amino acid carboxyl terminal peptide product that has a high degree of homology with VIP and PACAP. This novel peptide, which we have called GHRH-related peptide (GHRH-RP), has been previously localized to rat testicular germ cells. GHRH-RP activates Sertoli cell expression of stem cell factor. Although GHRH is produced by a variety of rat tissues, including the hypothalamus, placenta, testis, and ovary, GHRH-RP has only been described in the testis. We sought to determine if this novel peptide is present in the cycling rat ovary.

Characteristic expression of 105-kDa heat shock protein (HSP105) in various tissues of nonstressed and heat-stressed rats.

Although the induction of heat shock proteins (HSP) has been studied extensively in cultured cells, comparatively few studies have examined their expression in vivo. In this report, we investigated the expression and the state of 105-kDa heat shock protein (HSP105) in various tissues of rats, and found that two isoforms of HSP105 (HSP105-a and HSP105-b) were both moderately expressed in adrenal, spleen, liver and heart, and both increased markedly after heat shock. However, in brain HSP105-a was characteristically highly expressed over HSP105-b, but neither increased after heat shock. In addition, a 100-kDa protein (p100), a possible testis-specific HSP105 homologue was found in testis. When the effects of adrenaline and its antagonists on the heat-inducibility of HSP105 were examined, the induction of HSP105 in adrenal gland seemed to be negatively regulated through the alpha-adrenergic receptor. Furthermore, HSP105 was found to be associated with HSC70/HSP70, and to exist as high molecular mass complexes of 300-800-kDa and of 300-500-kDa in various tissues of nonstressed and heat-stressed rats, respectively. The molecular interaction between HSP105 and HSC70 suggests the possibility that HSP105 functions with HSC70 cooperatively in various tissues of rats.

P-160 - Effect of psychological stress on heat shock protein 70 levels in various tissues of rat

P-160 - Effect of psychological stress on heat shock protein 70 levels in various tissues of rat

P-389 - Polyamine levels in various tissues of rats treated with methotrexate and cyclophosphamide

P-389 - Polyamine levels in various tissues of rats treated with methotrexate and cyclophosphamide

Cardiac production and secretion of adrenomedullin are increased in heart failure.

Plasma adrenomedullin (AM) levels are reportedly increased in heart failure, but whether the cardiac production and secretion of AM is increased in heart failure remains unknown. To investigate the sites of production and secretion of AM in heart failure, we measured plasma AM levels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes AM into the circulation in patients with heart failure. We measured plasma and tissue AM levels by specific radioimmunoassay and AM mRNA by Northern blot analysis in rats with heart failure produced by aortocaval fistula. We also measured plasma AM levels in the coronary sinus and aorta in patients with left ventricular dysfunction before and after rapid right ventricular pacing. The increase in plasma AM levels in heart failure rats correlated with ventricular weight. Tissue AM levels were increased in the heart and lungs but not in the kidneys or adrenals of rats with heart failure. Similarly, tissue AM mRNA levels were also increased in the heart and lungs of heart failure rats. Plasma AM levels were higher in the coronary sinus than in the aorta in patients with left ventricular dysfunction. Rapid right ventricular pacing increased plasma atrial natriuretic peptide but not AM. These results suggest that plasma AM levels are increased in heart failure in proportion to the severity of heart failure and that cardiac production and secretion of AM is increased in heart failure rats. The lung may be another site for increased production of AM in heart failure rats. Human failing heart actually secretes AM into the circulation, and the regulation of AM secretion appears to differ from that of atrial natriuretic peptide.

Effects of dietary supplementation of N-acetylcysteine on cigarette smoke-related DNA adducts in rat tissues

Cigarette smoking plays a major role in the etiology of several human cancers. It is believed that formation of DNA adducts is an initial step in the carcinogenic process. In this study, we have examined the ability of dietary N-acetylcysteine (NAG) to inhibit the formation of cigarette smoke-related DNA adducts in various tissues of rats. Female Sprague-Dawley rats were exposed to cigarette smoke (10 mg TPM/m(3)) in a whole-body exposure chamber for 6 h per day, seven days a week for four weeks. The smoke-exposed groups were provided either an unrefined diet or diets supplemented with low (5,000 ppm) or high (20,000 ppm) dose of NAG. A sham group was given control diet and maintained on filtered ambient air. Tissue DNA analysis of smoke-exposed rats by nuclease P1-version of the P-32-postlabeling assay showed up to 6 adducts in the following descending order expressed as total adducts/10(10) nucleotides: 1 predominant (no. 5) and 4 (no. 1-no. 4) minor adducts in the (219 +/- 36), 6 minor adducts in the heart (93 +/- 11), 5 adducts in the trachea (50 +/- 16), and 4 adducts in the bladder (50 +/- 3.5); sham-treated animals showed 2 or 3 adducts in each tissue but at 4-20-fold lower levels. Dietary intervention with either high or low dose of NAC did not affect the levels of most adducts, except for the following: a 30-40% increase (P<0.05) for adducts 3 and 4 in the lung; a 40-50% decrease (P<0.05) for adduct 2 in the trachea; and a 30% increase (P<0.05) for adduct 2 in the bladder. In a second experiment conducted under identical conditions, most major and minor adducts remained unaffected with NAC intervention, except for adduct 2 in the trachea which was somewhat diminished. These results suggest that dietary NAC intervention does not significantly influence the levels of most major and minor adducts. However, some minor adducts in the lung, trachea and bladder were modulated differentially.

Plectin Transcript Diversity: Identification and Tissue Distribution of Variants with Distinct First Coding Exons and Rodless Isoforms

Plectin is a widely expressed protein that is very large in size and that has all the attributes of a multifunctional crosslinking and organizing element of the cytoskeleton. It displays a multidomain structure, versatile binding activities, and subcellular localizations that enable it to strengthen cells against mechanical stress forces. Moreover, hereditary gene defects in plectin cause epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with muscular dystrophy. Here we report the analysis of the exon–intron organization of the rat plectin gene and the identification of several different isoforms on the transcriptional level. We show that of 35 coding exons identified, 4 serve as alternative first exons splicing into the same successive exon 2, which is the first of 7 exons encoding a highly conserved actin-binding domain. RNase protection mapping of transcripts containing 3 of the identified 4 alternate first exons revealed their coexpression in rat glioma C6 cells and in a series of different rat tissues that we examined. Significant variations in expression levels of first exons indicated the possibility of tissue-specific promoter usage. In addition, plectin splice variants lacking exon 31 (>3 kb), which encodes the entire rod domain of the molecule, were identified in a variety of rat tissues. This study provides first insights into a complex plectin gene regulatory machinery with similarities to that of dystrophin.

Mechanism of expression of the rat HCNP precursor protein gene.

The hippocampal cholinergic neurostimulating peptide (HCNP), isolated from hippocampal tissue of 10- to 12-day-old rats, enhances the in vitro synthesis of acetylcholine in medial septal tissue explants. The HCNP precursor is a 21 kDa protein that binds hydrophobic ligands and Mg-ATP, and is associated with the opioid-binding protein. We employed an HCNP-precursor cDNA as probe to clone the genomic DNA, used for mapping of the exon-intron structure of the gene. We also determined the nucleotide structure of the promoter region of the rat HCNP precursor protein gene. By using S1 mapping and CAT as a reporter, we found multiple promoters that were aligned in the 5' untranslated region. In addition, the presence of several putative enhancer binding sequences were tested by electrophoresis mobility shift assays. Northern blot analysis revealed that the gene is expressed in a variety of rat tissues and various subregions of the brain. These results suggest that HCNP-precursor gene expression is regulated by a general transactivation factor such as SP1, and that the specific presence of the bioactive HCNP in certain tissues results from post-translational events such as proteolytic processing of the precursor protein, which takes place predominantly in the hippocampus of young rats.

Is alpha1D-adrenoceptor protein detectable in rat tissues?

We have used the alpha1D-adrenoceptor selective antagonist, BMY 7378, the alpha1D-selective agonists, adrenaline and phenylephrine, the alpha1A-selective antagonists, (+)-niguldipine, SB 216469 and WB4101, and the non-subtype-selective alpha1-adrenoceptor antagonist, nemonapride, to investigate the presence of alpha1D-adrenoceptors in rat tissues at the protein level. Radioligand binding studies using [3H]prazosin as the radioligand were performed in three tissues containing alpha1D-adrenoceptor mRNA, spleen, cerebral cortex and kidney, and in comparison in one tissue not containing alpha1D-adrenoceptor mRNA, liver. Cerebral cortex and kidney were also studied upon alpha1B-adrenoceptor inactivation by chloroethylclonidine treatment (10 microM, 30 min, 37 degrees C). Experiments with cloned rat alpha1-adrenoceptor subtypes transiently expressed in COS cells confirmed the known selectivity of the investigated drugs for alpha1-adrenoceptor subtypes or the lack thereof of nemonapride. Accordingly nemonapride had steep and monophasic competition curves in all native and chloroethylclonidine-treated tissues. BMY 7378 also had steep and monophasic competition curves and low affinity in all native tissues. In contrast, adrenaline and phenylephrine (in the presence of 100 microM GTP) had monophasic competition curves of low affinity in liver and spleen but biphasic competition curves in cerebral cortex and kidney. Following chloroethylclonidine treatment competition curves for adrenaline, phenylephrine, (+)-niguldipine, SB 216469 and WB 4101 remained biphasic in cerebral cortex and kidney while those for nemonapride remained monophasic. We conclude that alpha1D-adrenoceptors are not readily detectable at the protein level in a variety of rat tissues where their mRNA is expressed. The biphasic competition curves of some agonists and antagonists in chloroethylclonidine-treated rat tissues do not represent alpha1D-adrenoceptors and are not readily explained by the present alpha1A/alpha1B/alpha1D-adrenoceptor classification.

動物の尿酸分解酵素群に関する研究 : Ureidoglycollate lyase の進化

In lower animals such as marine invertebrates and crustaceans, urate is degraded to NH_3 and CO_2 as follows. Urate is degraded to allantoin by uricase (EC1.7.3.3); allantoin is then degraded by allantoinase (EC3.5.2.5) to allantoate, which is degraded to ureidoglycollate and urea by allantoicase (EC3.5.3.4). Ureidoglycollate is further degraded to glyoxylate and another molecule of urea by ureidoglycollate lyase (EC4.3.2.3). Urea formed is degraded to NH_3 and CO_2 by urease (EC3.5.1.5). However, the degradation of urate is much less complete in higher animals. It is generally accepted that during animal evolution, all of the urate degrading enzymes (uricase, allantoinase, allantoicase, ureidoglycollate lyase and urease) were lost in humans, anthropoid apes and New World monkeys, and all of the allantoin-degrading enzymes (allantoinase, allantoicase, ureidoglycollate lyase and urease) were lost in other mammals. However, surprisingly, ureidoglycollate lyase has been found in livers of rat, bovine and monkey, and in various tissues of rat. Ureidoglycollate lyase was highly purified and characterized from the heavy mitochondrial fraction of rat, bovine and monkey liver. The apparent Km values of the mammalian enzymes for ureidoglycollate were much higher than that of fish liver ureidoglycollate lyase. The mammalian enzymes differed from the fish liver enzyme in enzymic, physical and immunological properties.

Polyamine levels in various tissues of rats treated with 3-hydroxy-4-methoxycinnamic acid and 3,4-dimethoxycinnamic acid.

The effects of 3-hydroxy-4-methoxycinnamic acid (3H4MCA) and 3,4-dimethoxycinnamic acid (3,4DMCA) on body weight, organ weight, and the contents of putrescine, spermidine and spermine in 15 different tissues were examined in rats that had been given these compounds for 5 days. In 3H4MCA-treated rats, the weight of the spleen was significantly increased, while none of the other organs showed any significant changes. A diet containing either 3H4MCA or 3,4DMCA should not be taken by patients bearing cancers in the seminal vesicles, spleen or liver, and a diet containing 3,4DMCA should not be taken by patients bearing cancers in the testis, kidney, muscle, small intestine or brain (cortex) because of the significant increases in polyamines, which are associated with a risk of cancer growth, in these tissues. However, a diet containing 3H4MCA is recommended for the management of cancers in the skeletal muscle (femoral), tongue, small intestine (jejunum), stomach, lung and brain based on reductions in polyamines which stimulate tumor growth. A diet containing 3,4DMCA is also recommended for cancer in the prostate, thymus and stomach for the same reason. In addition, a synergic therapeutic effect for the treatment of cancers in these tissues may be anticipated by a combination of such a diet with anti-cancer drugs which reduce polyamine levels. The metastasis of cancers in these tissues may also be inhibited by the reduction of polyamines by these acids. The ratio of spermidine to spermine was significantly higher in the lung of 3H4MCA-treated rats, and lower in the seminal vesicle, thymus, kidney, heart, tongue, stomach and lung of 3,4DMCA-treated rats, than in control rats. The present experiment indicated that cancer patients should pay careful attention to endogenous polyamines in tissues bearing tumors induced by chemicals in ingesta and anti-cancer drugs, in addition to exogenous polyamines.

Insulin receptor content in tissues of normal and diabetic rats measured by radioimmunoassay

Insulin receptor (IR) content in different tissues has been quantitatively evaluated by means of steady state binding studies with radiolabeled insulin. The information provided by this approach, however, does not give a direct measurement of the receptor protein. Rather, it depends on the binding function of the IR, evaluated on the basis of curvilinear plots derived by Scatchard analysis of the experimental data. In the present report we employed a sensitive and specific radioimmunoassay (RIA) that allows a direct measurement of IR in solubilized cells or tissues. By this method we studied: a) IR distribution in several tissues of the rat, the animal model most frequently used in studies of insulin action; b) IR regulation in streptozotocin-treated, diabetic insulin deficient rats. Tissues from male Wistar rats (11 controls and 6 streptozotocin-treated diabetic animals) were homogenized, solubilized with Triton X-100 in the presence of protease inhibitors and stored at -80 C. IR content in the solubilized material was then measured by RIA. IR were detectable in all 11 tissues tested. Liver, kidney and brain neocortex had the highest IR content. (24.7 +/- 1.0, 20.5 +/- 1.1, 25.9 +/- 1.6 ng/mg protein, m +/- SE, respectively). As expected, circulating insulin levels were lower in diabetic rats than in control rats. In diabetic, insulin deficient rats, liver, kidney and skeletal muscle contained more IR than in control rats (p = 0.001; p = 0.018; p = 0.003, respectively), whereas IR content in neocortex was similar in the two groups. The IR RIA may represent a useful tool for the study of IR regulation and patho-physiology. Our data provide a comparative direct measurement of IR distribution in a variety of rat tissues. IR content in diabetic rats is increased in typical target organs for insulin action, as a consequence of up-regulation due to the reduced insulin levels. This is not the case for metabolically insulin-dependent tissues, like brain.

Disappearance of 125I-labelled myelin basic protein from blood circulation and its degradation and accumulation in various tissues in rats

Following acute central nervous system myelin injury, immunoreactive myelin basic protein (MBP) has been detected in the cerebrospinal fluid, blood and urine. In order to clarify the fate of MBP in the circulation, distribution and degradation of intravenously injected bovine MBP was followed in anaestethized rats for 5 to 240 min by using 125I-labelled MBP. Five minutes after injection of a dose of 60–400 ng of MBP, 44% of the label was recovered in the liver, 6.3% in the kidneys, 4.7% in the lungs and 15% in the blood circulation, the corresponding figures at a dose of 0.8 mg being 51, 7.4, 0.8 and 22%. The liver discarded the label fastest, 3% of the dose remaining 4 h after injection. The amount of label in urine increased simultaneously, the recovery at 4 h being 5.5% of the lower and 4.2% of the higher MBP dose. The percentage of total dose of the label per gram of tissue at 5 min (= distribution percentage, DP-5) was 3–4% in the liver and kidney and 1.6% in the spleen. The label content in the pancreas was increased at 15–60 min, compared to the DP-5 of 0.3% with a two-fold maximum at 30 min. The duodenum concentrated MBP in a similar manner as the pancreas but not as extensively. The DP-5 of 0.1% in the thymus was concentrated two-fold with a maximum at 60 min. A slight concentration occured in the heart. The DP-5 of 0.03% in muscle, testis and brain was concentrated 3-fold at 60 min, 3.6-fold at 60–240 min and 2-fold at 30–60 min in the aforementioned tissues, respectively. In spite of degradation of the label in tissues, the distribution of high molecular weight (HMW = TCA-precipitable) MBP was similar. Other experiments showed that the kidney, lung and duodenum contained most of the HMW MBP at 20 h. Upon continuous release of MBP, the pancrease, thymus, duodenum, muscle and testis would thus cumulatively concentrate MBP, and the kidney, lung and duodenum would be quantitatively most affected. MBP was previously shown to enter into cells of pancreative islets and to stimulate insulin and glucagon release. It could have biological effects in other tissues as well. These effects could explain some peripheral symptoms present in neurological disorders.

Aluminum polymeric implants: in vitro-in vivo evaluations.

The purpose of this investigation is to study the effect of long-term subcutaneous aluminum polymeric implants on aluminum release and accumulation in various tissues in rats. The implants were formulated using silicone rubber and polyurethane polymers and three different aluminum salts. The polymeric matrices were evaluated for in vitro release studies. These matrices released aluminum in vitro up to the period of four months. The aluminum matrices were implanted in rats and animals were sacrificed at various time intervals. Various tissues such as brain, kidney, liver, intestine, and heart were isolated. Aluminum in dried tissues was analyzed by Neutron Activation Analysis. Results from this investigation suggest that polymeric aluminum implants raise the aluminum concentration in the brain and liver. However, these implants did not increase aluminum levels in intestine, heart, and kidney. The polymeric aluminum implants could be used to establish an animal model for the neuropathology of dementia.

Nutritional regulation of gene expression of insulin-like growth factor-binding proteins and the acid-labile subunit in various tissues of rats

The plasma concentration and liver mRNA content of IGF-I are regulated by the quantity and quality of dietary proteins. To determine whether the synthesis of IGF-binding proteins (BPs) is also affected by protein nutrition, we assessed plasma concentration, tissue mRNA content and liver transcription rate of each BP after rats were fed either a 12% casein or a protein-free diet for 1 week. Protein deprivation reduced the plasma concentration of IGFBP-3 and IGFBP-4 and increased that of IGFBP-1 and IGFBP-2. The mRNA content in tissues and liver transcription rates of IGFBP-3 and IGFBP-4 did not change in response to protein deprivation although their plasma concentrations decreased. The increased plasma IGFBP-1 and IGFBP-2 concentrations were explained by the increased mRNA content and transcription rate of their genes in the liver. Although IGFBP-1 mRNA was increased by protein deprivation not only in liver but also in kidney, IGFBP-2 mRNA was increased only in liver and did not increase in any other tissue examined. In addition, the liver mRNA content of the acid-labile subunit, which can form a ternary complex with IGFs and IGFBP-3, was not affected by protein deprivation. These results show that tissue-specific synthesis of each BP is regulated in a distinct way in response to protein deprivation.

High-performance liquid chromatographic assay of propofol in human and rat plasma and fourteen rat tissues using electrochemical detection

This paper describes a sensitive HPLC-electrochemical detection analytical method for determining the concentration of the intravenous anesthetic, propofol, in human or rat plasma or serum and a variety of rat tissues. Internal standard and drug are extracted from serum or plasma and other tissues with pentane. 2,6- tert.-Butylmethylphenol is used as internal standard. It includes a novel steam distillation procedure for separating the highly lipophilic propofol from skin and fat. The plasma/serum assay has a precision of 1–4% (C.V.) in the range 10 ng/ml to 1 μg/ml and permits the assay of 5 ng/ml from 0.1 ml of plasma/serum. The tissue procedure allows the estimation of 50 ng/g in 0.1 g of tissue for most of the major organs with less than 2% (C.V.) precision. This assay was used to measure propofol concentrations in plasma/serum and tissue samples in support of a project to develop a physiological pharmacokinetic model for propofol in the rat.

Effect of protein nutrition on insulin-like growth factor-I (IGF-I) receptor in various tissues of rats.

The effects of protein nutrition on insulin-like growth factor-I (IGF-I) receptor in various tissues of rats were investigated. Northern blot and dot blot hybridization analyses were performed using RNA from testis, heart, lung, intestine, stomach, kidney, and brain of rats fed on a 12% casein diet, on a 12% gluten diet which was marginally deficient in lysine and threonine, or on a protein-free diet. The mRNA content of IGF-I receptor in the testis and heart of the rats fed on the 12% gluten and protein-free diets was significantly larger than those of the rats fed on the 12% casein diet. Whereas in other tissues examined, IGF-I receptor mRNA content did not change significantly under the different nutritional conditions. The amount of IGF-I receptor in these tissues and the affinity to IGF-I were determined by measuring the amount of 125I-labelled-IGF-I bound to solubilized IGF-I receptor. The affinity of IGF-I receptor to IGF-I in each tissue under the various nutritional conditions did not show any marked differences. The number of receptors did not change in the testis, lung, intestine, brain or kidney; possibly increased in stomach of the rats fed on the 12% gluten or protein-free diet; and slightly decreased in heart of the rats fed on the 12% gluten diet compared with that of the rats fed on the 12% casein diet. These results indicate that the synthesis of IGF-I receptor is regulated in a distinctive way in each tissue in response to protein nutrition, and suggest that the regulation may have some physiological meaning in signal transmission of IGF-I. The amount of IGF-I receptor, however, was relatively constant in most tissues. Because the plasma IGF-I and IGF-binding protein concentrations change dramatically under different nutritional conditions, we conclude that concentrations of plasma IGF-I and IGF-binding proteins may mainly regulate the IGF-I action in tissues in response to protein nutrition.