Biomedical subjects

J T Cheng

Publications and source records attributed to J T Cheng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Changes in endogenous monoamines in aged rats.

1. It has been documented that ageing may alter endogenous neurotransmitters. However, these results are controversial. Thus, in the present study, cerebral cortex and plasma from male Wistar rats aged 8 weeks and 6, 12 or 24 months were used to investigate the changes in monoamines using electrochemical detection. 2. A marked decrease in L-dihydroxyphenylalanine (L-DOPA) was observed in aged rats. Like the decrease in dopamine (DA), levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA), the major metabolite of 5-HT, in aged rats were decreased in the cerebral cortex and plasma. Plasma levels of noradrenaline and levels of adrenaline in the cerebral cortex were also decreased in aged rats. Moreover, levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolite of DA, in the cerebral cortex and plasma were reduced by ageing. The level of homovanillic acid (HVA) in all samples was markedly increased with ageing. 3. The ratio of DOPAC/DA and 5-HIAA/5-HT, being closely linked with the activity of monoamine oxidase, was increased in the cerebral cortex and plasma with ageing. The ratio of HVA/DOPAC, an index of the activity of catechol-O-methyltransferase, was also higher in the cerebral cortex and plasma of aged rats. 4. These data suggest that ageing may alter endogenous monoamines in both the brain and peripheral tissues.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Protein kinase C and changes in manganese superoxide dismutase gene expression in cultured glial cells.

1. To study the role of protein kinase C (PKC) in the increase in manganese superoxide dismutase (Mn-SOD) gene expression following transient hypoxia in glial cells, we examined the mRNA levels of Mn-SOD using northern blot analysis. 2. The Mn-SOD mRNA levels were markedly increased after exposure to nitrogen gas for 5 min. 3. Pretreatment with chelerythrine or GF109203x, inhibitors of PKC, attenuated the increase in Mn-SOD mRNA following hypoxia in a concentration-dependent manner. 4. Incubation with phorbol 12-myristate 13-acetate, the PKC activator, enhanced the increase in Mn-SOD gene expression in response to transient hypoxia. 5. The results suggest that hypoxia increases Mn-SOD gene expression in cultured glial cells mainly through activation of a PKC pathway.

Cell Hypoxia↗

PubMed2001

Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in streptozotocin-induced diabetic rats.

In an attempt to elucidate the effect of vanadium compounds on the gene expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally administrated at the dose of 1 mg/kg body weight into streptozotocin-induced diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked lowering of plasma glucose with a significant decrease of food and water intake in these STZ-diabetic rats treated with VOSO4, although the weight gain was unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide concentration, in STZ-diabetic rats was also reduced by this oral treatment of VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the feeding behavior and hypothalamic NPY gene expression. These data suggest that decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery of hyperphagia in diabetic rats lacking insulin.

Animals↗

PubMed2001

Release of beta-endorphin by prostaglandin E2 to lower plasma glucose in streptozotocin-induced diabetic rats.

In the present study, Wistar rats, which received a streptozotocin injection to induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate the effect of prostaglandin (PG) E2 on plasma glucose. Intravenous injection of PGE2 produced a dose-dependent lowering of plasma glucose level in fasting STZ-diabetic rats after 60 min. In addition to the blockade of this hypoglycemic effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin at a dose effective to block alpha1-adrenoceptors abolished the action of PGE2. An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE2 injections. Participation of sympathetic stimulation by PGE2 may thus be speculated. Also, the plasma glucose-lowering effect of PGE2 was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid mu-receptor. Injection of PGE2 increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by prazosin. Bilateral adrenalectomy resulted in the loss of this PGE2 effect, and no increase was seen in plasma BER with PGE2 in STZ-diabetic rats. Therefore, beta-endorphin from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats by PGE2 through an increase of NE release to activate alpha1-adrenoceptors.

Adrenalectomy↗

PubMed2001

Increase of opioid mu-receptor gene expression in streptozotocin-induced diabetic rats.

Opioids play an important role in the regulation of glucose homeostasis. In the previous report, we showed that activation of opioid mu-receptors produced a plasma glucose lowering effect in diabetic rats lacking insulin. In the present study, we found that the response of opioid mu-receptor is more sensitive in streptozotocin-induced diabetic rats (STZ-diabetic rats) than in normal rats. Intravenous injection of loperamide, an agonist of opioid mu-receptors, induced a dose-dependent decrease of plasma glucose from 3 microg/kg to 60 microg/kg in fasting STZ-diabetic rats. However, loperamide decreased the plasma glucose of normal fasting rats at the doses of 0.3 mg/kg to 1.5 mg/kg, which were much higher than those needed to produce the same effect in diabetic rats. The plasma glucose-lowering action of loperamide at the dose effective in normal rats disappeared in opioid mu-receptor knockout mice, while the plasma glucose-lowering response to loperamide was still observed in wild-type mice. This opens the possibility of mediation through opioid mu-receptor in the plasma glucose-lowering action of loperamide. Moreover, the mRNA level of opioid mu-receptor in the liver markedly increased in STZ-diabetic rats compared to normal rats. Normalization of plasma glucose concentrations in STZ-diabetic rats with exogenous insulin or phlorizin reversed mRNA and protein levels of opioid mu-receptor in the liver after 4 days of treatment. This shows that correction of hyperglycemia in STZ-diabetic rats may reverse the higher gene expression of opioid mu-receptor. These results suggest that hyperglycemia is responsible for increase of opioid mu-receptor in STZ-diabetic rats.

Animals↗

PubMed2001

Inhibitory effect of stevioside on calcium influx to produce antihypertension.

Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.

Animals↗

PubMed2001

Metformin-like effects of Quei Fu Di Huang Wan, a Chinese herbal mixture, on streptozotocin-induced diabetic rat.

Effect on plasma glucose concentration of Quei Fu Di Huang Wan (Quei Fu DHW), the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, was investigated in diabetic rats deficient in insulin. Changes of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats) receiving repeated oral administration of Quei Fu DHW were determined. Also, the mRNA level (by Northern blotting) and protein level (by Western blotting) of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were measured to compare differences between groups receiving repeated oral administration of Quei Fu DHW, metformin, and two active herbs (Zou Guei or Fuzei) at effective dosages. In STZ-diabetic rats, acute oral administration of Quei Fu DHW decreased the plasma glucose level significantly in a dose-dependent manner from 5 mg/kg to 26.0 mg/kg. Similar treatment with Quei Fu DHW also brought on a plasma glucose-lowering effect in normal rats, although the effectiveness was not as significant as in STZ-diabetic rats. Repeated oral treatment of Quei Fu DHW at 26 mg/kg every 8 h, three times daily for 3 days, produced a plasma glucose-lowering activity similar to that of metformin-treatment in STZ-diabetic rats. Oral administration of Zou Guei (Cinnamomi Cortex) or Fuzei (Aconiti Tuber), the individual constituent of Quei Fu DHW, at the dose of 50 mg/kg into STZ-diabetic rats for 3 days normalized hyperglycemia. Similar to the repeated treatment with Quei Fu DHW, Fuzei at the effective dose reversed the elevated mRNA and protein levels of PEPCK in liver from STZ-diabetic rats. This is consistent with findings that metformin restored the increased gene expression of PEPCK in liver from STZ-diabetic rats. However, the gene expression of PEPCK in STZ-diabetic rats was not influenced by similar treatment with Zou Guei. The present study found that oral administration of Quei Fu DHW could decrease hepatic gluconeogenesis in a way similar to metformin in lowering plasma glucose in diabetic rats lacking insulin. Thus, this preparation may be a helpful adjuvant for the treatment of diabetic disorders in clinical practice.

Animals↗

PubMed2001

Stimulation of insulin release in rats by Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine.

Die-Huang-Wan is a herbal mixture widely used in Chinese traditional medicine to treat diabetic disorders. We have investigated the effect of Die-Huang-Wan on plasma glucose concentration in-vivo. Die-Huang-Wan was administered orally (5.0, 15.0 or 26.0 mg kg(-1)) to three rat models. Wistar rats were used as the normal animal model, rats with insulin-resistance (induced by the repeated thrice daily injection of human long-acting insulin) were used as the non-insulin-dependent diabetic model, and streptozotocin-induced diabetic rats were used as the insulin-dependent diabetic model. In normal rats, approximately 1 h after oral administration of Die-Huang-Wan the plasma glucose concentration decreased significantly in a dose-dependent manner, from 5 to 26.0 mg kg(-1). A similar effect was observed in rats with insulin-resistance. However, this effect was not observed in streptozotocin-induced diabetic rats, even at an oral dose of 26.0 mg kg(-1). These results suggested an insulin-dependent action, a view supported by the increase of plasma insulin-like immunoreactivity in normal rats receiving Die-Huang-Wan. The results indicated that Die-Huang-Wan had an ability to stimulate the secretion of insulin and this preparation seemed helpful in improving the diabetic condition, especially hyperglycaemia in type-II diabetes.

Animals↗

PubMed2001

Genetic variation of the nucleocapsid genes of waterfowl parvovirus.

Duck parvovirus (DPV) and Goose parvovirus (GPV) isolated from infected waterfowls with Derzsy's disease in the year 1999 were identified by polymerase chain reaction and sequencing. The nucleotide sequences of their viral capsid proteins (VPs) show that they share 77% similarity at the DNA, and 84.6% at the protein level. The most variable region between DPV and GPV resides in the N-terminal of VP2 before the initiation codon of VP3 with 35% (19/54) amino acids divergence. Viral capsid protein sequences diverge 4.1 to 4.4% among 1990-99 isolated strains. Variant amino acids cluster in the common regions of VP3 at residues 203-266 and 482-534 which overlaps with the regions proposed to expose on the outer surfaces of parvoviral particles, implying that selective pressure from host immune system might play a part. These data provide useful information for antigenic epitope prediction. This study also reveal the presence of conserved strain-specific residues in VPs and these residues seldom vary among different viral isolates, suggesting that they might be functionally important and worth further investigation.

Amino Acid Sequence↗

PubMed2001

Plasma glucose-lowering effect of tramadol in streptozotocin-induced diabetic rats.

The effect of tramadol on the plasma glucose level of streptozotocin (STZ)-induced diabetic rats was investigated. A dose-dependent lowering of plasma glucose was seen in the fasting STZ-induced diabetic rats 30 min after intravenous injection of tramadol. This effect of tramadol was abolished by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid mu-receptors. However, response to tramadol was not changed in STZ-induced diabetic rats receiving p-chlorophenylalanine at a dose sufficient to deplete endogenous 5-hydroxytrptamine (5-HT). Therefore, mediation of 5-HT in this action of tramadol is ruled out. In isolated soleus muscle, tramadol enhanced the uptake of radioactive glucose in a concentration-dependent manner. The stimulatory effects of tramadol on glycogen synthesis were also seen in hepatocytes isolated from STZ-induced diabetic rats. The blockade of these actions by naloxone and naloxonazine indicated the mediation of opioid mu-receptors. The mRNA and protein levels of the subtype 4 form of glucose transporter in soleus muscle were increased after repeated treatments for 4 days with tramadol in STZ-induced diabetic rats. Moreover, similar repeated treatments with tramadol reversed the elevated mRNA and protein levels of phosphoenolpyruvate carboxykinase in the liver of STZ-induced diabetic rats. These results suggest that activation of opioid mu-receptors by tramadol can increase the utilization of glucose and/or decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.

Animals↗

PubMed2001

Modest overexpression of neuropeptide Y in the brain leads to obesity after high-sucrose feeding.

Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in feeding and body weight regulation. However, there is little genetic evidence that overexpression or knockout of the NPY gene leads to altered body weight regulation. Previously, we developed NPY-overexpressing mice by using the Thy-1 promoter, which restricts NPY expression strictly within neurons in the central nervous system, but we failed to observe the obese phenotype in the heterozygote. Here we report that in the homozygous mice, overexpression of NPY leads to an obese phenotype, but only after appropriate dietary exposure. NPY-overexpressing mice exhibited significantly increased body weight gain with transiently increased food intake after 50% sucrose--loaded diet, and later they developed hyperglycemia and hyperinsulinemia without altered glucose excursion during 1 year of our observation period.

Aging↗

PubMed2001

Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.

Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.

Animals↗

PubMed2000

Insulin restores neuronal nitric oxide synthase expression in streptozotocin-induced diabetic rats.

Nitric oxide (NO) is known to play an important role in the pathophysiology of insulin-dependent diabetic mellitus (IDDM). In an attempt to investigate the relation between insulin and NO in IDDM, the present study employed male Wistar rats to induce IDDM by intravenous injection of streptozotocin (STZ). Four groups of rats were used; untreated normal control group, insulin treated STZ group, vehicle-treated STZ control, and one group of age-matched rats which were orally supplied with glucose to increase plasma glucose (glucose-challenged rats). Changes of the activity and gene expression of neuronal nitric oxide synthase (nNOS) were examined in cerebellum and kidney of these groups. The activity of nNOS in cerebellum, determined by conversion of [3H] L-arginine to [3H] L-citrulline, in STZ-induced diabetic rats was markedly lower than normal rats. Insulin treatment reversed the nNOS activity. Similar reversion by insulin treatment was also obtained in the gene expression of nNOS. However, the activity and gene expression of nNOS in glucose-challenged rats were not different from those in normal rats. The role of hyperglycemia can thus be ruled out. These findings indicated that an impairment of nNOS in the brain of rats with IDDM is mainly due to the absence of insulin.

Animals↗

PubMed2000

Gene expression of alpha(1A)-adrenoceptor but not alpha(1B)-adrenoceptor in cultured myoblast C(2)C(12) cells of mice.

Subtypes of alpha(1)-adrenoceptor (alpha(1)-AR) in the cultured myoblast C(2)C(12) cells have been examined using molecular biological identifications. Expression of the two distinct mRNAs that encode proteins of alpha(1A)- and alpha(1B)-AR was studied using reverse transcription combined with polymerase chain reaction (RT-PCR). Results of RT-PCR demonstrated a marked expression of alpha(1A)-AR in the prostate of rats. Samples from the C(2)C(12) cells under the same amount of amplification showed the expression of alpha(1A)-AR at a level slightly lower than that from the prostate of rats. Western blotting analysis using receptor subtype-specific antibody also indicated that the alpha(1A)-AR was expressed in C(2)C(12) cells as well as in prostate of rats. However, although the expression of alpha(1B)-AR was obtained in the spleen of rats, expression of alpha(1B)-AR was undetectable in the C(2)C(12) cells either the results of RT-PCR or the Western blotting analysis. The present study suggests that alpha(1A)-AR is a major subtype of alpha(1)-AR in the C(2)C(12) cell line.

Animals↗

PubMed2000

Role of alpha1A-adrenoceptor in the regulation of glucose uptake into white adipocyte of rats in vitro.

In an attempt to know the functional role of alpha1A-adrenoceptors in adipose tissue, white adipocytes (WAT) of Wistar rats were used to investigate the change of glucose uptake after pharmacological activation of alpha1-adrenoceptors. Methoxamine enhanced the uptake of radioactive glucose into isolated WAT in a concentration-dependent manner. Translocation of glucose transporter (GLUT4) from cytosol to membrane was also stimulated with methoxamine. Action of methoxamine to raise glucose uptake was abolished in WAT pre-incubated with the antagonists, both tamsulosin and WB 4101, at concentrations sufficient to block alpha1A-adrenoceptors. However, chlorethylclonidine (CEC). the antagonist of alpha1B-adrenoceptors, showed the inhibition of methoxamine-induced action only at a higher concentration. Even under the treatment with maximal concentration of CEC, methoxamine can produce action about 80% of the vehicle-treated control. The major role of alpha1A-adrenoceptors in the stimulation of glucose uptake by methoxamine can thus be considered. In the presence of specific inhibitor of phospholipase C (PLC), U73312, methoxamine-stimulated glucose uptake into WAT was reduced in a concentration-dependent manner and U73343, the negative control of U73312, did not affect the action of methoxamine. Moreover, chelerythrine and GF 109203X diminished the methoxamine-stimulated glucose uptake at a concentration sufficient to inhibit protein kinase C (PKC). Inhibition of phosphoinositide-3 kinase (PI-3 kinase) by LY294002 also abolished methoxamine-stimulated glucose uptake. Therefore. the obtained data suggest that an activation of alpha1A-adrenoceptors, presence in WAT, by agonist and/or neurotransmitter may increase the glucose uptake via PLC-PKC pathway and the activation of PI-3 kinase.

Adipocytes↗

PubMed2000

Activation of adenosine A1 receptors by drugs to lower plasma glucose in streptozotocin-induced diabetic rats.

To examine the role of the adenosine A1 receptor in glucose regulation in the absence of insulin, the present study investigated the changes of plasma glucose in male streptozotocin-induced diabetic rats (STZ-diabetic rats) using dipyridamole to increase endogenous adenosine and N6-cyclopentyladenosine (CPA) to activate the adenosine A1 receptor. Intravenous injections of dipyridamole or CPA induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats. Plasma glucose lowering action of dipyridamole, like that of CPA, was inhibited in a dose-dependent manner by pre-treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or 8-(p-sulfophenyl)theophylline (8-SPT) at which block the adenosine A1 receptors. Action of the adenosine A1 receptors can thus be considered. In isolated skeletal muscle, CPA enhanced the glucose uptake in a concentration-dependent manner. Blockade of this action by DPCPX and 8-SPT again supported the mediation of the adenosine A1 receptor. Also, CPA produced an increase of glycogen synthesis in isolated soleus muscle. Moreover, CPA decreased plasma triglyceride and cholesterol levels significantly in STZ-diabetic rats. These results suggest that activation of adenosine A1 receptors can increase glucose utilization in peripheral tissues by increasing tissue uptake and glycogen synthesis to lower plasma glucose in rats lacking insulin.

Adenosine↗

PubMed2000

Gastric mucosal damage induced by arecoline seizure in rats.

In an attempt to know the relation of seizure and gastric mucosal damage, we challenged arecoline (ACL) centrally to induce seizure and investigated gastric hemorrhagic injury in acid-irrigated stomachs of rats. The protective effects of several drugs also were evaluated. After deprivation of food for 24 h, rats were received laparotomy under diethylether-anesthesia. Both pylorus sphincters and carotid esophagus were ligated. The forestomach was equipped with a cannula for gastric irrigation. After recovery from anesthesia (approximately 1 h), the stomach was irrigated for 2 h with an acid solution containing 100 mM HCl and 54 mM NaCl or the same volume of normal saline. Intracerebroventricular (i.c.v.) ACL (0, 1, 3 or 10 mg/kg dissolved in 10 microl of CSF) was challenged to rats immediately after gastric irrigation. The seizure in rats was produced by ACL in a dose-related manner. The ulcerogenic parameters such as decrease of gastric mucosal glutathione levels and increase of histamine concentrations and lipid peroxide generations as well as the raise of luminal hemoglobin contents and exacerbated mucosal lesions were obtained depending on the doses of ACL challenged. These ulcerogenic parameters produced in ACL (10 mg/kg, i.c.v.) seizure rats were markedly ameliorated by gastric vagotomy or central anticholinergics. Intraperitoneal ketotifen, zinc sulfate, diphenhydramine or cimetidine also produced significant (p<0.05) inhibitions of these ulcerogenic parameters in ACL seizure rats. In conclusion, central ACL seizure may produce gastric oxidative stress and hemorrhagic lesions via vagal nervous activation and histamine release in acid-irrigated stomachs of rats.

Animals↗

PubMed2000

Alterations in beta-adrenergic receptor density and adenylate cyclase activity in the rat brain treated chronically with lead.

Behavioral and memory impairment resulting from lead exposure is well known but the mechanism is not. We utilized the brain of lead exposed rats to investigate this problem. In an effort to elucidate the mechanism responsible for this alteration we examined blood and brain lead levels, brain beta-adrenoceptor density and cyclic AMP production in lead exposed rats. Wistar rats used in these trials were divided into six groups of ten animals each. Five groups were given drinking water containing 0.05, 0.1, 0.5, 1 and 2% lead acetate for a period of 60 days. One group (control group, 0% lead acetate) was given pure water. Application of a trend test indicated that both blood and brain lead levels increased significantly from group 0% to group 2% (group 0% <group 0.05% <group 0.1% <group 0. 5%<group 1%<group 2%), but that brain beta-adrenoceptor density and cyclic AMP levels stimulated by isoproterenol decreased (group 2%<group 1%<group 0.5%<group 0.1%<group 0.05%<group 0%). Kd did not vary among the six groups and this indicated that the affinity of the remaining beta-adrenoceptors for [125I]iodocyanopindolol was not changed. Linear regression analysis showed that beta-adrenoceptor density and stimulated cyclic AMP level in brain was found to be negatively correlated with brain lead level (P<0.001). The results show lead exposure that may be the result of an alteration of beta-adrenergic receptor and adenylate cyclase activity in brain.

Adenylyl Cyclases↗