A high affinity GTP binding site in rat brain

In conscious cats with gastric fistulas, 10 μg · kg^?1 of human urinary gastric inhibitor (HUGI) given as an intravenous bolus injection increased mean rectal temperature 1.4°C and inhibited mean gastrin-stimulated acid secretion by 64%. The sample of HUGI contained an amount of β-hydroxymyristic acid corresponding to a 5% contamination of the HUGI with bacterial endotoxin. Injection of bacterial endotoxin in an amount corresponding to the β-hydroxymyristic acid content of HUGI mimicked, both in magnitude and time course, the increase in body temperature and the inhibition of acid secretion produced by HUGI. We conclude that inhibition of acid secretion by HUGI may be due to the presence of an endotoxin-like contaminant.     

Role of 5-hydroxytryptamine in the modulation of acoustic brainstem (far-field) potentials.

Acoustic brainstem evoked responses (far-field) were recorded in rats anesthetized witha-chloralose, subsequent to pharmacological modification of serotonergic activity. Reserpine caused an initial decrement followed by an increment in FFP amplitudes, probably as a result of initial displacement followed by depletion of 5HT from its storage sites. Depletion of 5HT by PCPA also caused an amplitude increment, whereas increased 5HT levels following 5HTP administration resulted in an amplitude decrement. It is suggested that 5HT may be an inhibitory transmitter in pontine and mesencephalic brainstem relays of the auditory pathway.     

High affinity binding of [3H]ethylketocyclazocine to rat brain homogenate

Ethylketocyclazocine (Ekc), a potent κ-receptor agonist, binds to opiate receptor sites in rat brain tissue. The binding was saturable with respect to the concentration of [³H]Ekc. The dissociation constant of Ekc-receptor complex was 1.8 nM and the maximum number of binding sites in the whole brain was 9.6 pmol/g of tissue. Opiate agonists and antagonists have a high affinity for [³H]Ekc binding sites, but results of present investigations failed to differentiate opiates thought to be specific for the μ- and κ-receptors.     

Effect of repeated dietary exposure of aflatoxin B1 on brain biogenic amines and metabolites in the rat

Male Sprague-Dawley rats were treated po twice weekly for 3 weeks with a low (32.8 micrograms/kg) and high dose (327.9 micrograms/kg) of aflatoxin B1 (AFB1) in corn oil. A control group received corn oil only. At the end of the experiment the rats were killed, and the concentrations of the brain catecholamines, norepinephrine (NE) and dopamine (DA), catecholamine metabolites, 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), and the indoleamine serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined by high-pressure liquid chromatography in five brain regions. The major effects were found in striatal dopamine and serotonin concentrations, with decreases of 37 and 29%, respectively. A corresponding decline was observed in the dopamine metabolites, homovanillic acid (44%) and dihydroxyphenylacetic acid (30%). Concentrations of these neurotransmitters and metabolites were only marginally altered in cerebral cortex, cerebellum, hypothalamus, and medulla oblongata. It appears that a major effect of AFB1 is on dopaminergic pathways, possible by selectively perturbing the conversion of tyrosine to biogenic catecholamine neurotransmitters.     

Local application of cyclic AMP in the rat brain: characterization of the cardiovascular response

Previous studies have demonstrated that central administration of dibutyryl cyclic AMP (DBcAMP) produces a dose-dependent rise in blood pressure accompanied by tachycardia. In an attempt to delineate brain sites that mediate these cardiovascular responses, DBcAMP was stereotaxically injected into local brain areas. Injections of 100 micrograms into the right lateral, third, and fourth ventricles produced pressor responses. Perfusion of the brain from the lateral ventricle to the cisterna magna with 15 micrograms/25 microliters per min induced a rise in blood pressure and significant bradycardia. The cyclic nucleotide was injected unilaterally in doses of 10, 25, and 50 micrograms into the posterior hypothalamic nucleus (PHN), anterior hypothalamic area (AHA), locus coeruleus (LC), and nucleus tractus solitarii (NTS). PHN injections induced tachycardia with minimal changes in blood pressure. Bradycardia and a depressor response were observed following injection of the 10 micrograms dose into the LC. Within the AHA, DBcAMP (10 micrograms) did not induce significant changes in cardiovascular function. Additionally, injections into the NTS initiated a biphasic depressor-pressor effect. Within these sites, cardiovascular responses to the 10 micrograms dose of DBcAMP paralleled those observed after adrenergic activation. These results strongly suggest that cyclic AMP functions as a second messenger within select central cardiovascular regulatory sites and plays an important role in cardiovascular regulation.     

High-affinity binding of [3H]doxepin to histamine H1-receptors in rat brain: Possible identification of a subclass of histamine H1-receptors

The binding of the radioactively labeled tricyclic antidepressant, [³H]doxepin, to rat brain tissie was examined. Scatchard plots of specific [³H]doxepin binding indicated the presence of two distinct binding sites. The equilibrium dissociation constant (K_D) of the high-affinity site was 0.020 nM with a maximal binding capacity (B_max) of 13.7 fmol/mg protein. The corresponding values for the low-affinity site were 3.6 nM and 740 fmol/mg protein, respectively. The high-affinity site was sensitive to competition by pharmacologically relevant concentrations of histamine H₁ antagonists such as pyrilamine (K_D = 1.0 nM), diphenhydramine (K_D = 20 nM), d-chlorpheniramine (K_D = 1.7 nM), and 1-chlorpheniramine (K_D = 97 nM). The B_max for [³H]doxepin binding in the high-affinity H₁-receptor, however, was approximately 10% of the B_max obtained using [³H]pyrilamine to label the H₁-receptor. Various tricyclic antidepressants were very potent inhibitors at the high-affinity [³H]doxepin site. Their potencies, however, did not correlated with their potencies previously reported for the H₁-receptor. The regional distribution of [³H]doxepin high-affinity sites correlated with the known distribution of H₁-receptors in the rat brain. These results suggest that [³H]doxepin is binding to a subclass of histamine H₁-receptors.     

Stimulation of rat C6 glioma ecto-5'-nucleotidase by chronic ethanol treatment

Treatment of rat C6 glioma cells in culture with 100 mM ethanol led to increased ecto-5'-nucleotidase activity. Studies were performed to obtain information on the mechanism(s) of action for this effect. Growth of C6 glioma cells in 100 mM ethanol for 6 days increased ecto-5'-nucleotidase activity but had no effect on the pH optima or substrate specificity of the ecto-enzyme. A comparison of enzyme activity of intact cells with that of disrupted cells revealed a selective stimulation of the ecto-enzyme, i.e. the enzyme on the outer plasma membrane. Kinetic studies of cells continuously treated with 100 mM ethanol for 6 days showed an apparent increase in affinity of the ecto-enzyme for 5'-AMP, with no appreciable change in the maximum velocity (V_max). The concentration-dependent inhibition of ecto-5'-nucleotidase activity by Concanavalin A (Con A) was antagonized by ethanol treatment. Double reciprocal plot analysis showed that ethanol acted in an apparently noncompetitive manner with respect to Con A inhibition. It appears that the availability of the catalytic site of the ecto-5'-nucleotidase to exogenous substrates was increased. The data are consistent with rearrangement of the plasma membrane resulting from continuous exposure to ethanol.