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C B Pert

Publications and source records attributed to C B Pert.

At least 55 records · Page 3Linked to original sources
PubMed1987

Autoradiographic visualization of sex differences in the pattern and density of opiate receptors in hamster hypothalamus.

Slide-mounted brain sections were used to visualize the distribution of opiate receptors in the hypothalamus of male and female hamsters using the vitro film autoradiography. Sex differences were found in the binding density and patterns of [3H]naloxone-labeled receptors. The distribution and density of [3H][D-Ala2,D-Leu5]enkephalin-labeled delta-receptors in adjacent brain sections were similar in males and females. Male hamsters showed a U-shaped pattern of [3H]naloxone binding in the sexually dimorphic nuclear complex with 28% and 34% greater labeling of the sexually dimorphic nucleus (SDN) and bed nucleus/stria terminalis (BNST), respectively, than periovulatory estrous females. Estrous and diestrous females showed a V-shaped pattern of [3H]naloxone binding in the same region, but binding density was higher at diestrus. Greater specific [3H]naloxone binding in diestrous females was also evident following extensive prewashing of slide-mounted tissue sections indicating that residual endogenous opioids were not occupying receptors, and thus, reducing the labeling of receptors in tissue from estrous females. An estrous-linked change in the affinity of hypothalamic opiate receptors was suggested by findings that [3H]naloxone binding density was greater in tissue from diestrous females when incubations were conducted in the presence of a 1-nM, but not a 10-nM, concentration of the labeled antagonist. Finally, a dense are of [3H]naloxone binding was discovered in the dorso-suprachiasmatic region of the hypothalamus. These data provide evidence for a sexual dimorphism in the distribution and density of opiate receptors in hamsters. The data suggest that mu- or kappa-receptors are more likely than delta-receptors to be involved in mediating hypothalamic effects of endogenous and exogenous opioids on reproductive functions in this species.

Animals↗
PubMed1987

Visualization and characterization of interleukin 1 receptors in brain.

Interleukin 1 (IL 1) is a polypeptide hormone produced by macrophages, keratinocytes, and brain glial cells which acts as a soluble mediator in immunological and inflammatory reactions. Although its best known effect on the central nervous system is its ability to cause fever, it has been found to influence cell growth, food intake, and slow-wave sleep. We have developed a binding assay for 125I-labeled recombinant murine IL 1 and show it to be highly specific. Additionally, affinity cross-linking studies indicate that the rat brain IL 1 receptor has a m.w. of approximately 80,000, which is similar to the previously described recognition molecule on T cells and fibroblasts. Using autoradiographic techniques, we visualized the distribution of 125I-IL 1 binding in sections of fresh frozen rat brain. IL 1 receptors were found to be widespread throughout the brain, forming a distinctive pattern of distribution. Areas especially dense in receptors were typically neuron-rich sites of the brain such as granule cell layer of the dentate gyrus, the pyramidal cell layer of the hippocampus, and the granule cell layer of the cerebellum as well as in the hypothalamus. The pattern of IL 1 receptor distribution indicates the presence of receptors on neuron cell bodies and the localization to numerous discrete brain areas other than those hypothalamic sites involved in temperature regulation, suggesting a broader role for IL 1 in brain functioning than previously recognized. IL 1, derived from local or systemic sources, may function in the brain to coordinate behavioral and neuroendocrine activities with immunological and inflammatory reactions throughout the body.

Animals↗
PubMed1987

The pattern of [3H]cyclofoxy retention in rat brain after in vivo injection corresponds to the in vitro opiate receptor distribution.

Cyclofoxy, a fluorinated analog of naltrexone, has been designed specifically to permit in vivo labeling of opiate receptors in experimental animals and ultimately, humans. Recently, using positron emission tomography (PET), 3-[18F]acetylcyclofoxy was shown to accumulate in opiate receptor-rich brain regions of a live baboon and to be stereospecifically displaced by injections of (-)-naloxone but not (+)-naloxone. Autoradiographic evidence is presented here that the unacetylated compound, [3H]cyclofoxy, labels a population of opiate receptors in brain after in vivo injections that is virtually identical to that labeled by [3H]naloxone. The in vivo binding patterns of [3H]cyclofoxy in brain were similar to those obtained following incubation of slide-mounted brain sections in vitro. Intravenous injections of [3H]cyclofoxy to rats yielded high (greater than 4:1) striatal and thalamic to cerebellar binding ratios in brain homogenates, supernatants and in 24 micron-thick brain sections 60 min after 30 mu Ci per animal (spec. act. = 16.4 Ci/mmol). Autoradiographs revealed the typical opiate antagonist binding profile with marked retention of [3H]cyclofoxy in the striatal patches, subcallosal streak, medial habenula and central thalamus with little retention of label in cerebellum. [3H]Cyclofoxy binding was reversible since the radiolabeled drug disappeared from brain tissue within 2 h after injections to rats, or could be removed from brain slices in vitro by washing slide-mounted tissue sections for 45 min. In addition, after in vitro washing the same brain sections again bound [3H]cyclofoxy or [3H]naloxone in the same pattern. When pre-washed brain sections were incubated with [3H]cyclofoxy in the presence of unlabeled naloxone, [3H]cyclofoxy binding was reduced to background levels. These data show that [3H]cyclofoxy labels-sensitive opiate receptors in vivo and in vitro. The present results combined with evidence that cyclofoxy demonstrates a low level of toxicity in animals suggest that cyclofoxy is an excellent tool with which to study the physiological role of opiate receptors in living animals using in vivo autoradiography, and in humans using PET.

Animals↗
PubMed1987

CD4 receptor binding peptides that block HIV infectivity cause human monocyte chemotaxis. Relationship to vasoactive intestinal polypeptide.

The octapeptide Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr (peptide T) and two structural analogs are potent agonists of human monocyte chemotaxis, evincing identical rank potency orders as was previously shown for their inhibition of human immunodeficiency virus (HIV) envelope binding and T cell infectivity. Chemotactic activity could be inhibited by anti-CD4 monoclonal antibodies (Mabs), but not other mononuclear cell Mabs. The core peptide required for chemotactic activity is a pentapeptide related to the sequence Thr-Thr-Asn-Tyr-Thr. Homologous pentapeptides, identified by computer search, were detected in several other non-HIV-related viruses as well as the neuropeptide vasoactive intestinal polypeptide (VIP). The CD4 molecule, therefore, appears to be a recognition molecule for a small signal peptide ligand whose active sequence is a homolog of peptide T and which may be the neuropeptide VIP.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Vasoactive intestinal peptide 1-12: a ligand for the CD4 (T4)/human immunodeficiency virus receptor.

A five-amino-acid (TDNYT) sequence of vasoactive intestinal polypeptide (VIP) shares homology with the proposed attachment sequences of the human immunodeficiency virus (HIV). Synthetic peptides with these sequences have previously been shown to block viral envelope (gp120) binding and HIV infectivity and to serve as agonists of the CD4 (or T4) receptor. Utilizing an in vitro human monocyte chemotaxis bioassay we examined novel synthetic VIP and gp120 sequences and characterized their pharmacological activities on monocyte chemotaxis. CD4 receptor activity is primarily specified by N-terminal (VIP [1-12]) amino acids. The profound immunosuppression of AIDS is not easily explained solely by virus infection. Recently described immunological functions of VIP are similar to some of the immunological abnormalities shown by patients with AIDS. An overproduction of a VIP-like molecule from viral sources (e.g. gp120) could explain some of the immune system impairments which have been described in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Structure-activity studies of C- and N-terminal fragments of cholecystokinin 26-33 in guinea pig isolated tissues.

In vitro structure-activity studies with cholecystokinin (CCK)/gastrin-related peptides, including C- and N-terminal fragments of CCK 26-33, were undertaken in guinea pig gallbladder and ileum. The general order of potency in both smooth muscle preparations is CCK 26-33 greater than CCK 1-33 greater than 27-33 much much greater than nonsulfated (NS) CCK 26-33 greater than pentagastrin greater than CCK 30-33. None of the CCK fragments exhibit antagonistic properties such as in guinea pig, rat and mouse pancreatic acinar cells and hog duodenum. These observations suggest the existence of CCK receptor sub-types in peripheral tissues.

Animals↗
PubMed1987

High-affinity substance P binding sites in rat esophagus plexus submucosus.

Substance P receptors were investigated in rat esophagus using 125I-Bolton-Hunter substance P as a labeling probe. Autoradiographic studies show that esophageal submucosa contains clusters of high-affinity substance P binding sites [maximum binding (Bmax) 4.2 +/- 0.28 fmol/mg protein; dissociation constant (Kd) 0.1 +/- 0.01 X 10(9) M]. The receptor distribution pattern is typical for submucous neurons. These data suggest that substance P may act as a neurotransmitter in rat esophagus.

Animals↗
PubMed1987

Autoradiographic localization of T4 antigen, the HIV receptor, in human brain.

Using a novel autoradiographic technique and a monoclonal antibody to T4, the entry protein for the AIDS virus HIV, we have determined the distribution of T4 in selected areas of the human brain. T4 was found throughout the human brain in a pattern similar to that seen in squirrel monkey and rat, thus demonstrating a conservation of both the antigen and the antigen distribution. T4 was especially abundant in emotion-mediating areas, such as the hippocampus, which are typically enriched with neuropeptide receptors. In addition, several regions of the cerebral cortex were found to have T4 antigen especially in superficial layers. These data suggest that the psychiatric and neuropathological symptoms presented by AIDS patients may be a result of the direct interaction of the AIDS virus with specific areas of the brain.

Antibodies, Monoclonal↗
PubMed1987

Visualization of cytokine and virus receptors common to the immune and central nervous system.

Interleukin 1 (IL-1) and the human retrovirus HTLV-III/LAV represent two distinct molecular and biological constituents that are apparently shared by both the immune and central nervous systems. IL-1 is a cytokine produced principally by monocytes of the immune system and glial cells of brain in situ or in vitro. HTLV-III/LAV represents a unique class of human retrovirus which is the recognized etiological vector of acquired immunodeficiency syndrome (AIDS) which exhibits cellular tropism to helper T lymphocytes or brain by the interactions with an entry protein previously described as the T4 antigen. Autoradiography was used to examine the specific binding distribution of 125I-IL-1 alpha and anti-T4 antibody to rat and squirrel monkey brain sections, respectively. Representative data shows unique neuroanatomical distributions of the IL-1 binding protein (receptor) and the T4 antigen in brain. The autoradiographic study provides a qualitative and quantitative analysis of shared receptors between the immune and nervous systems and offers potential for the discovery of new biological or pathological interactions of these common physiological constituents.

Animals↗
PubMed1987

Enkephalins, catecholamines, and psychological mood alterations: effects of prolonged exercise.

Seven healthy trained men were studied to determine if running at various relative intensities [percent maximal oxygen consumption (VO2max)] alters peripheral venous levels of leucine enkephalin-like material. Enkephalins were measured using a radio-receptor assay (Leu-Enk RRA). Subjects ran for 80 min at 40 and 60% VO2max and for 40 min at 80% VO2max. Each session was separated by at least 1 wk. Heart rate, blood pressure, lactic acid, and rectal temperature responses increased in an intensity-dependent manner. Epinephrine increased from resting values of 38.2 +/- 6.8 pg X ml-1, mean +/- SE to 75.0 +/- 13.3 pg X ml-1 during the 40% VO2max run, from 60.2 +/- 15 to 186 +/- 45 pg X ml-1 during the 60% run, and from 33.4 +/- 7.6 to 311 +/- 52 pg X ml-1 at the 40th min of the highest workload (80% VO2max). These increases were significant (P less than 0.05). Plasma Leu-Enk RRA was between 3.8 and 6.2 pmol X ml-1 prior to each run and did not change significantly as a result of exercise. Levels of Leu-Enk RRA also did not change during 30 min of supine recovery. Perception of effort increased (P less than 0.05) with increases in exercise intensity, and effort sense was unrelated to plasma Leu-Enk RRA. Psychological tension decreased significantly (P less than 0.05) following exercise at 60 and 80% of VO2max, but the decrease following the 40% run was not significant (P greater than 0.05). Reduced tension following exercise was not related to Leu-Enk RRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Bombesin in human and guinea pig alveolar macrophages.

Bombesin found in neuroepithelial bodies and oat cell carcinoma of the lung, is thought to play an important role in normally developing and malignant lung. Monocytes-macrophages and human small cell lung carcinoma cells share several features, including macrophage-specific surface markers and the expression of functional receptors for bombesin-like neuropeptides and growth factors. Because small cell lung carcinoma cells synthesize immunoreactive bombesin, we investigated the possibility that alveolar macrophages also contain bombesin, a plausible hypothesis considering the many reports of neuropeptide production by immune cells and cells of bone marrow origin. Adherent human peripheral blood mononuclear cells as well as human and guinea pig alveolar macrophages were found to contain bombesin. The peptide was detected by radioimmunoassay, immunohistochemistry, high-pressure liquid chromatography with the use of different monospecific antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas.

The binding of 125I-labeled insulin in thin sections of frozen fresh rat brain (95% specific binding) was shown using autoradiography. By several criteria including structure-activity relationship analysis, the brain insulin receptors were qualitatively indistinguishable from insulin receptors previously characterized on brain and other more typical target tissues and distinct from receptors for the insulin-like growth factors. The 125I-labeled insulin binding sites in brain formed a distinct pattern with high levels of binding in all olfactory areas and in closely related limbic regions. Binding was also prominent in the neocortex and the accessory motor areas of the basal ganglia and the cerebellum. Among ancillary brain structures only the choroid plexus demonstrated a high density of insulin receptors. When insulin receptors were located on cortical or laminated structures, the highest binding occurred in the superficial ("molecular" or "plexiform") layer, i.e. the layer which receives afferent input and/or is rich in the dendritic branches of principal neurons (e.g. external plexiform layer of the olfactory bulb and the molecular layer of the dentate gyrus). The enrichment of insulin receptors in the olfactory and limbic systems, which is a characteristic feature of other known neuropeptides, in addition to their prevalence in the strata occupied by the dendritic fields of principle neurons, suggests a neuromodulatory function for insulin in the brain.

Animals↗
PubMed1986

Interferon gamma and granulocyte/macrophage colony-stimulating factor inhibit growth and induce antigens characteristic of myeloid differentiation in small-cell lung cancer cell lines.

The expression of several macrophage and hemopoietic cell surface markers recently described on small-cell lung cancer (SCLC) cell lines was studied by use of flow cytometry. The antigens Leu-M3, Leu-7, and HLA-DR were examined for their modulation by human interferon gamma and granulocyte/macrophage colony-stimulating factor (GM-CSF). Both of these lymphokines generally induced enhanced expression of hemopoietic markers in several SCLC lines. A differential response to these two hormones was observed, in that qualitative and quantitative differences in marker modulation among the tested cell lines were apparent. In addition to regulating the antigenic phenotype of these cells, both interferon gamma and GM-CSF had antiproliferative effects on SCLC lines as determined by [3H]thymidine incorporation and clonal growth in agar. These results suggest that interferon gamma and GM-CSF promote a differentiation process in SCLC cell lines that has characteristics in common with myeloid differentiation. These findings support the theory that SCLC tumors are hemopoietic cells that arise from macrophages or their precursors and suggest new therapeutic modalities for the treatment of lung cancer.

Antigens, Neoplasm↗