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Biomedical subjects

C B Pert

Publications and source records attributed to C B Pert.

At least 127 records · Page 7Linked to original sources
PubMed1982

Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality.

A general technique is described for using slide-mounted unfixed tissue sections to characterize and visualize drug and neurotransmitter receptors in brain or other tissues. The preparation of material, from fresh frozen, unfixed brain to dried sections securely attached to slides, is described in detail. The tissue can be kept intact during incubation at varying temperatures in solutions containing radiolabeled ligand, ions, buffers, and allosteric effectors. Strategies are described for determining optimal stereospecific binding with highest signal-to-noise ratios and for determining that a "meaningful" receptor is being studied. Dry formaldehyde fixation by vapors from heated paraformaldehyde preserves the tissue quality and traps the ligand near its site on the receptor, permitting subsequent histological processing through alcohols, solvents, and aqueous media, including liquid nuclear track emulsion. Visualization of [3H]naloxone- or [3H]enkephalin-labeled opiate receptor distributions in rat and human brains is achieved by tritium-sensitive film or by classical "wet" emulsion autoradiography. The advantages of the film include its ease of use and the ability to quantify receptor density by densitometry which can be computer-assisted. The advantage of the emulsion is the greater resolution and the concomitant appearance of morphology in cell-stained sections. Examples of correlations of opiate receptor distributions which underlying cytoarchitecture illustrate the potential for receptor localization studies.

Animals↗
PubMed1981

High levels of intracellular bombesin characterize human small-cell lung carcinoma.

"Small cells" or "oat cells" characterize a virulent form of lung cancer and share many biochemical properties with peptide-secreting neurones. The neuropeptide bombesin is present in all small-cell lines examined, but not in other lung cancer cell lines, suggesting that bombesinergic precursor cells in lung may give rise to this disease.

Adenocarcinoma↗
PubMed1981

Alterations in rat central nervous system endorphins following transauricular electroacupuncture.

Auricular electro-stimulation (electroacupuncture) was found to produce naloxone-reversible analgesia in the rat. These behavioral effects were accompanied by significant increases in cerebrospinal fluid (CSF) levels of endorphins with concomitant decreases in the basomedial hypothalamus and medial thalamus of beta-endorphin-like immunoreactivity as well as endorphin-like radioreceptor activity. In addition, the radioreceptor assay also revealed a decrease in endorphin-like radioreceptor activity in the periaqueductal gray (PAG) matter. These results are interpreted to imply that electroacupuncture in the rat produces at least part of its analgesic action by activating central nervous system endorphinergic circuitry which results in a release and depletion of endorphins in certain brain loci and a concomitant elevation in the CSF. Hypophyseal endorphins do not appear to be involved in mediating acupuncture-induced analgesia in the rat since plasma levels of endorphins were not altered by this manipulation.

Acupuncture Therapy↗
PubMed1981

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

Animals↗
PubMed1981

Effects of guanine nucleotides on CNS neuropeptide receptors.

The effect of nucleotides on central nervous system neuropeptide receptor binding was investigated. The guanine nucleotides, guanosine-5'-triphosphate and guanylyl-5'-imidodiphosphate, significantly inhibited the binding of radiolabeled vasoactive intestinal polypeptide but not that of [Tyr4]bombesin to rat brain membranes. Vasoactive intestinal polypeptide binding was inhibited by guanine nucleotides in a dose-dependent manner. Using a 20 microM dose, 60% of the specific vasoactive intestinal polypeptide binding was inhibited by guanylyl-5'-imido-diphosphate, which was more potent than guanosine-5'-triphosphate, whereas other nucleotides were not effective. This reduction in binding was a consequence of lower affinity of the receptor for vasoactive intestinal polypeptide, which in turn resulted from an increased rate of dissociation.

Animals↗
PubMed1981

Ontogeny of opiate receptors in rat forebrain: visualization by in vitro autoradiography.

The embryonic and postnatal ontogeny of opiate receptors in rat telencephalon was mapped by in vitro autoradiographic localization of [3H]naloxone and [3H]enkephalin binding. Opiate receptors marked by naloxone binding first appear at embryonic day 14 in the striatum, rapidly proliferate to adult densities and at the time of birth, gradually become reorganized into the adult heterogeneous pattern of receptor-rich patches surrounded by sparse, diffuse labeling in the rest of the striatum. The enkephalin binding in the striatum appears later in embryonic development and gradually increases in density to form the rather homogeneous adult pattern. Naloxone binding in the paleocortical olfactory areas appears early also, densely within the molecular layer as soon as it is formed at E16. This density is only temporary, as labeling just after birth falls to low adult levels in all areas except portions of the amygdala. Receptors disappear also in the islands of Calleja and the pallidum. Naloxone binding in the septum and neocortex appears gradually in development. The early appearance of striatal and paleocortical [3H]naloxone-labeled opiate receptors and their localization within the subependymal zones suggest that receptors appear on immature neurons before and during migration and, therefore, may influence the intricate patterns of connections that later form. The delayed appearance of the [3H]enkephalin-labeled receptors may reflect the dependence of the peptide binding on later developing molecules of adenylate cyclase.

Aging↗
PubMed1981

Interconverting mu and delta forms of the opiate receptor in rat striatal patches.

The binding of a radiolabeled "mu receptor" prototype opiate, dihydromorphine (H2morphine), and the binding of a "delta receptor" prototype, [D-Ala2,D-Leu5]enkephalin (D-Enk), to slide-mounted rat caudate slices were simultaneously compared quantitatively and visualized by autoradiography. Generally, D-Enk bound to opiate receptors distributed evenly throughout the entire striatum (type 2 pattern), whereas H2morphine labeled discrete islands or patches of receptors (type 1 pattern). In the presence of Mn2+ (3 mM) or other divalent cations, however, Na+ and GTP at 25 degrees C caused an increase in D-Enk binding at the expense of H2morphine binding at striatal opiate receptor patches. Thus, these conditions shifted D-Enk binding from an even pattern to one that included both an even and patchy distribution. These incubation conditions not only promoted D-Enk binding to striatal patches but also enabled the opiate receptor to regulate adenylate cyclase with the same (P less than 0.01) ligand selectivity pattern as that obtained by the displacement of D-Enk binding. The relative affinity of opiate receptors in striatal patches for opiate peptides, naloxone, and morphine appears to be a function of incubation conditions and coupling to adenylate cyclase and is not indicative of distinctly different opiate receptors. We postulate a three-state allosteric model consisting of mu agonist-, mu antagonists-, and adenylate cyclase-coupled delta-agonist-preferring states, whose equilibrium may be regulated by a sulfhydryl group mechanism.

Adenylyl Cyclases↗
PubMed1981

Phencyclidine (angel dust)/sigma "opiate" receptor: visualization by tritium-sensitive film.

[3H]Phencyclidine ([3H]PCP) binds specifically to an apparently single class of binding sites on slide-mounted sections of rat olfactory bulb (Kd = 46 nM; Bmax = 10.5 fmol per slice). Bound [3H]PCP can be displaced by nonradioactive PCP and a series of its analogs with relative potencies that correlate closely (P less than 0.001) with values determined in a rat discrimination test that utilized PCP as a cue. Although morphine, naloxone, and opiate peptides do not displace bound [3H]PCP, psychotomimetic benzomorphans, classed as "sigma opiates," are quite potent displacers in vitro and have PCP-like behavioral properties in vivo. These results suggest that phencyclidine and the sigma opiates act at the same sites. [3H]PCP binding sites were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry and color coding. The [3H]PCP binds most densely to cortical areas, diffusely in neocortex, and somewhat heterogeneously in the laminae of the hippocampal formation and dentate gyrus. Most of the brainstem and spinal cord show low specific [3H]PCP binding, with gray matter generally showing more binding than white.

Animals↗
PubMed1980

Increased renal neuroleptic binding in spontaneously hypertensive rats.

The present experiments demonstrate high affinity stereospecific binding of the dopaminergic ligand [3H]spiroperidol to rat renal membranes. The binding was saturable, regionally distributed, and showed the same specificity as the caudate [3H]spiroperidol site for displacement by dopaminergic antagonists. Since there is an association between hypertension and abnormalities of renal blood flow, which appears to be regulated in part by dopamine, [3H]spiroperidol binding was measured in kidneys of spontaneously hypertensive rats. In two independent experiments renal cortical [3H]spiroperidol stereospecific binding was increased in spontaneously hypertensive rats.

Animals↗