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Biomedical subjects

C B Pert

Publications and source records attributed to C B Pert.

At least 109 records · Page 6Linked to original sources
PubMed1983

Inhibition of dopamine-activated adenylate cyclase and dopamine binding by opiate receptors in rat striatum.

Low-affinity (micromolar) 3H-dopamine binding was measured under conditions which permitted dopamine activation and opiate inhibition of adenylate cyclase in rat striatal membranes. Opiate drugs and peptides inhibited the dopamine binding in the presence of both GTP and Gpp(NH)p. Opiate inhibition of adenylate cyclase was, however, observed only in the presence of GTP. It is suggested that the dopamine D1 receptor in striatum may be modulated by the opiate delta receptor through a shared guanine nucleotide binding subunit.

Adenylyl Cyclase Inhibitors↗
PubMed1983

Comparative pharmacological properties and autoradiographic distribution of [3H]ethylketocyclazocine binding sites in rat and guinea pig brain.

[3H]Ethylketocyclazocine (EKC) binds to a single class of sites under various incubation conditions in both rat and guinea pig brain. Ligand selectivity patterns strongly suggest that [3H]EKC binds to kappa opiate receptors in both species and under both incubation conditions. Moreover, the autoradiographic distribution of [3H]EKC binding sites is very similar under both incubation conditions. In guinea pig brain, [3H]EKC binding sites are highly concentrated in deep layers of the cortex, caudate-putamen, and nucleus accumbens. In rat brain, kappa opiate receptors are mainly found in caudate-putamen, nucleus accumbens, amygdala, and thalamus. [3H]EKC binding sites are not concentrated in deep layers of the cortex in rat brain. Thus, the autoradiographic distribution of kappa opiate receptors is species-dependent.

Analgesics, Opioid↗
PubMed1983

The distribution of cholecystokinin and vasoactive intestinal peptide in rhesus monkey brain as determined by radioimmunoassay.

The concentration of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in dissected cortical and subcortical areas of four rhesus monkeys' brains was determined by radioimmunoassay (RIA). Cerebral cortical samples from one human brain are included for comparison. Preliminary data from two baboon brains are described. The results are similar to previous studies on rat (1-7), human (7-12), porcine (12,13), bovine (3) and guinea pig brains (14) and indicate that: 1) both CCK and VIP are widely distributed in cortical and subcortical areas in these species, 2) CCK is generally more abundant than VIP in primate brain, and 3) the distribution of CCK and VIP in the rat brain parallel those in infrahuman primate and human brain.

Animals↗
PubMed1983

Binding of radiolabeled opiates to slide-mounted sections of molded minced rat brain: a novel method for conducting radioreceptor assays.

To facilitate the quantitative study of the opiate receptor, we have developed a novel variation of the ligand binding technique. The binding of 3H-opiates to rat brain membranes is compared with the binding to slide-mounted sections of molded minced rat brain. The latter method is characterized by a high signal and a superior signal-to-noise ratio over a wide range of ligand concentrations. The results are discussed in reference to other ligand binding methodologies.

Animals↗
PubMed1983

Properties of the phencyclidine (PCP) receptors.

[3H]Phencyclidine (PCP, Angel Dust) receptors have been characterized using a rat brain binding section technique. [3H]PCP labels a single class of site in rat brain (KD = 46 nM; Bmax = 10.5 fmol/slice). Ligand selectivity pattern strongly suggests that [3H]PCP binds to sites relevant for its pharmacological actions. Chronic PCP treatment (10 mg/kg/day for 14 days) decreases the number of sites (Bmax) for [3H]PCP and [3H]spiperone binding but not for [3H]dihydromorphine. These modifications could be related to the development of tolerance and dependence to PCP. Visualization of [3H]PCP binding sites shows high densities of receptors in cortical areas and hippocampus. Lower densities are observed in caudate-putamen, nucleus accumbens, and amygdala. Negligible quantities of receptors are seen in brain stem and over white matter. The presence of specific [3H]PCP binding sites in rat brain suggests the possible existence of an endogenous ligand for this unique receptor.

Animals↗
PubMed1983

Synthesis and pharmacological characterization of (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6,7-benzomorphan (fluorophen), a ligand suitable for visualization of opiate receptors in vivo.

A fluorinated derivative of the benzomorphan opiate agonist phenazocine, (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6, 7-benzomorphan (fluorophen), was prepared by N-acylation of (+/-)-5,9 alpha-dimethyl-2'-hydroxybenzomorphan with (p-fluorophenyl)acetyl chloride, followed by diborane reduction of the resulting amide. Fluorination produces only a twofold opiate receptor affinity loss when measured either by bioassay or receptor binding (selectivity mu congruent to delta greater than kappa). Labeled with 18F, fluorophen should be sufficiently potent to be useful as an in vivo probe for visualizing opiate receptors by positron emission transaxial tomography (PETT).

Animals↗
PubMed1983

Phencyclidine ("angel dust") analogs and sigma opiate benzomorphans cause cerebral arterial spasm.

Several psychotomimetic phencyclidine (PCP) analogs--N-ethyl-l-phenylcyclohexylamine (PCE), N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), N-[1-(thienyl)cyclohexyl ))pyrrolidine (THP), ketamine, and N,N-dimethyl-l-phenyl-cyclohexylamine (PCDEA)--were tested on basilar and middle cerebral arteries of the dog in vitro and found to induce contraction in these blood vessels with a maximal contractile activity (i.e., intrinsic activity) similar to that of PCP. The concentration-effect curves of these compounds were found to be parallel to the curve of PCP (P less than 0.01). The relative potency was PCE greater than TCP greater than PCP greater than THP greater than PCDEA greater than ketamine. A PCP analog with no psychotomimetic activity, 1-piperidinocyclohexanecarbonitrile (PCC), did not induce the blood vessels to contract, nor did the opiate morphine. Three psychotomimetic benzomorphans--pentazocine, cyclazocine, and N-allylnorcyclazocine--were found to: (i) also produce contraction; and (ii) have concentration--effect curves parallel to the curve of PCP, but with reduced intrinsic activities (i.e., maximal tensions were lowered) compared to PCP. A kappa opiate, ethylketocyclazocine, relaxed the blood vessels in a dose-dependent manner. This study provides direct evidence for a distinct PCP receptor on cerebral blood vessels and suggests that certain benzomorphans may produce cerebral vasospasm via PCP-receptor interactions.

Animals↗
PubMed1982

Visualization and solubilization of rat brain opiate receptors with a "kappa" ligand selectivity pattern.

1. Specific binding of [3H]ethylketocyclazocine (EkappaC), a prototype kappa-opiate agonist, to slide-mounted rat striatal sections is increased in the presence of 100 mM NaCl at 4 degrees C. 2. Under similar incubation conditions, binding of mu and delta prototype opiates is reduced to almost undetectable levels. 3. Correlation (P less than 0.01) of the ligand selectivity pattern of [3H]EKC displacement with the potencies of various opiate drugs in inhibiting the contractions of the rabbit vas deferens, a kappa-opiate receptor bioassay, suggests that the binding site under study represents the pharmacologically relevant kappa-opiate receptor. 4. Visualization of these kappa-opiate receptors with tritium-sensitive film reveals a striking, highly discrete brain distribution pattern (e.g., striatal patches, habenular stripe) which is similar to that of [3H]dihydromorphine and [3H]naloxone. 5. Soluble [3H]EKC binding sites obtained from rat membranes also possess a kappa-like ligand selectivity pattern, with bremazocine being a potent displacer while mu and delta ligands are almost inactive. 6. A possible explanation of these data is that the "kappa"-opiate binding site in rat brain is one transitional state of an opiate receptor capable of assuming distinct conformations with characteristic ligand selectivity patterns. Other possibilities such as pre and post-synaptic locations should also be considered.

Animals↗
PubMed1982

Chronic phencyclidine treatment decreases phencyclidine and dopamine receptors in rat brain.

Chronic phencyclidine treatment (10 mg/kg/day, SC for 14 days) significantly decreased the number of [3H]phencyclidine and [3H]spiperone binding sites in rat brain. [3H]Dihydromorphine binding was not affected by the same treatment. An acute treatment with phencyclidine (10 mg/kg, SC) did not modify any of the binding sites under study. These results suggest that a chronic phencyclidine treatment induces a down-regulation of phencyclidine and dopamine receptors without affecting opiate receptors. These reductions in the number of phencyclidine and dopamine binding sites might be related to the development of tolerance and/or dependence to phencyclidine.

Animals↗
PubMed1982

Corticotropin and beta-endorphin-like materials are native to unicellular organisms.

Multiple molecular forms of immunoreactive corticotropin (ACTH) and beta-endorphin were present in extracts of a unicellular eukaryote (Tetrahymena pyriformis). One form of immunoreactive ACTH reacted similarly with two different ACTH antisera (one specific for the 11-24 sequence and the other with determinants within sequences 1-14 and 17-39) and migrated with synthetic hACTH-(1-39) in a gel filtration system. This form also exhibited ACTH bioactivity in a dispersed rat adrenal cell bioassay system, with a mean immunoassay/bioassay ratio of 1.5. Gel filtration revealed multiple size classes of immunoreactive beta-endorphin; a major peak of radioreceptor activity was detected which exhibited a K(av) similar to that of authentic beta-endorphin. A major portion of immunoreactive beta-endorphin-sized material exhibited retention times similar to those of synthetic human and camel beta-endorphin upon reverse-phase high-pressure liquid chromatography. These distinctive properties and specificities would seem to exclude the presence of limited homologies with sequences present in other proteins. High molecular weight material containing both ACTH and beta-endorphin antigenic determinants was also demonstrated, suggesting, but not proving, the presence of a common precursor molecule.

Journal Article↗
PubMed1982

Correlation of regional brain metabolism with receptor localization during ketamine anesthesia: combined autoradiographic 2-[3H]deoxy-D-glucose receptor binding technique.

LKB film autoradiography of 2-]3H]deoxy-D-glucose uptake shows that ketamine, administered in anesthetic doses, alters the pattern of metabolic activity in rat hippocampus. The labeled metabolic marker can be washed out of the slide-mounted tissue sections by preincubation to permit in vitro autoradiography of drug and neurotransmitter receptors in the same animal. In this way, opiate and phencyclidine receptor distributions may be correlated with patterns of glucose utilization in adjacent sections. If the observed relative enhancement of 2-deoxy-D-glucose uptake in the stratum moleculare of hippocampus reflects elevated metabolism in nerve terminals there, then the binding of ketamine to phencyclidine receptors on neurons in distant afferent sites, such as entorhinal cortex, may initiate the physiologic and metabolic effects.

Animals↗