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Biomedical subjects

R B Innis

Publications and source records attributed to R B Innis.

At least 127 records · Page 7Linked to original sources
PubMed1983

Autoradiographic localization of cholecystokinin receptors in rodent brain.

Cholecystokinin (CCK) receptor binding sites have been localized by autoradiography in the guinea pig and rat central nervous system. [125I]CCK-triacontatriapeptide labeled the sites in brain slices with an observed association constant equal to 0.041 min-1 and a dissociation constant equal to 0.008 min-1. CCK-triacontatriapeptide (CCK-33) and the C-terminal octapeptide of CCK-33 (CCK-8) potently inhibited [125I]CCK-33 binding with Ki's of 2 nM, whereas desulfated CCK-8 (CCK8-ds) and the C-terminal tetrapeptide of CCK-33 (CCK-4) were much weaker. Receptors were concentrated in the olfactory bulb, in the superficial laminae of the primary olfactory cortex, in the deep laminae of the cerebral cortex, and in the pretectal area. Substantial numbers of sites were also found in the basal ganglia, in the amygdala, and in the hippocampal formation. [125I]CCK-33 binding sites appear to be located on fibers of the optic tract and probably on olfactory tract fibers as well. These results are discussed in terms of physiological functions associated with CCK, presynaptic receptors, and axonal flow of CCK receptors.

Animals↗
PubMed1981

Diffuse enkephalin innervation from caudate to globus pallidus.

The source of enkephalin in neuronal terminals of the rat globus pallidus was evaluated with electrolytic and knife cut lesions. Straight knife cuts medial to the globus pallidus or a curved knife cut just below the corpus callosum do not reduce immunofluorescence staining in the globus pallidus, indicating that cerebral cortex is not a major source of pallidal enkephalin. Electrolytic lesions of dorsal and ventral portions of the globus pallidus, and even lesions which sever medial from lateral globus, fail to reduce pallidal staining, ruling out long enkephalin neurons traversing the globus. Large electrolytic lesions of the head of the caudate do decrease dorsal pallidal fluorescence, though multiple small caudate lesions are without observable effect. Large pallidal lesions elicit a build-up of enkephalin fluorescence in the caudate. These results suggest that the caudate is the sole source of pallidal enkephalin and that the innervation diffusely converges on the smaller globus pallidus.

Animals↗
PubMed1981

[3H]Bradykinin receptor binding in mammalian tissue membranes.

[3H]Bradykinin binds to membranes from a variety of mammalian tissues in a saturable fashion with a dissociation constant of about 5 nM. Highest levels of binding are detected in guinea pig ileum, colon, and duodenum and in the oestrus rat uterus. The relative potencies of bradykinin derivatives in competing for these binding sites in guinea pig ileum membranes correlate with their contractile potencies in the ileum better than with contractile effects in the uterus. Thus, receptor recognition sites may differ in ileum and uterus. Monovalent and divalent cations at physiological concentrations reduce [3H]bradykinin binding. Of the monovalent cations, medium lowers binding 50% at about 80 mM. Among the divalent cations, calcium lowers binding about 50% at 5 mM, suggesting a link to the calcium conductance channel.

Animals↗
PubMed1981

Multiple neurotransmitter receptors in the brain: amines, adenosine, and cholecystokinin.

Radioligand binding studies of neurotransmitter receptors have provided discrimination at the molecular level, permitting the differentiation of multiple receptor subtypes for several biogenic amines. Using this paradigm we have labeled two distinct receptors each for cholecystokinin (CCK) and for adenosine. Adenosine receptors were labeled in brain with [3H]N6-cyclohexyladenosine (3H-CHA) and [3H]1,3-diethyl-8-phenylxanthine (3H-DP). The adenosine receptor labeled by 3H-CHA appears to be an A1 site, associated with reduction of adenylate cyclase activity, while 3H-DP sites resemble A2 receptors linked to adenylate cyclase enhancement. Cholecystokinin-33 labeled by the Bolton-Hunter procedure with 125I(125I-BH-CCK) labels different receptors in brain and pancreas. The pancreatic receptor does not react with CCK derivatives of fewer than eight amino acids, while the brain receptor does recognize pentagastrin, the carboxyl-terminal five amino acids of CCK. The "brain type" CCK receptor may normally interact with CCK-4, the carboxyl-terminal tetrapeptide of CCK, recently identified as a unique neuropeptide highly concentrated in the brain. CCK-8, the other major molecular form of CCK, may be the endogenous ligand for the "pancreatic type" receptor.

Adenosine↗
PubMed1980

Fluorescent probes of alpha- and beta-adrenergic and opiate receptors: biochemical and histochemical evaluation.

Dansyl derivatives of the opiate antagonist naloxazone and the alpha-adrenergic blocking drug 2-[2',6'-dimethoxy)phenoxyethylamino]methyl-benzodioxan (WB-4101) were synthesized as potential in vivo fluorescent labels for opiate and alpha-adrenergic receptors, respectively. When assayed in vitro dansyl analogs display Ki-values for [3H]naloxone and [3H]WB-4101 binding of 8 nM and 80 nM, respectively. The same patterns of histofluorescence are observed in rat brain slices after the intravenous or intracerebroventricular injection of both dansyl drugs. The same patterns are also observed in dansyl-propranolol and 9-aminoacridine-propranolol (9-AAPN) treated animals as well as in untreated control rats. Accordingly, the observed fluorescence does not reflect the labeling of any receptor but is consistent with the distribution of lipofuscin, an endogenous fluorescent compound.

Adrenergic alpha-Antagonists↗
PubMed1980

Distinct cholecystokinin receptors in brain and pancreas.

125I-Labeled (Bolton-Hunter) cholecystokinin triacontatriapeptide (CCK-33) binds saturably and reversibly to distinct receptors in brain and pancreatic membranes. The peptide specificity of pancreatic CCK binding is the same as that for pancreatic amylase release. In brain, gastrin and pentagastrin display nanomolar affinity for binding sites, whereas in pancreas these two peptides are virtually inactive. Though these differences indicate that brain and pancreas possess distinct CCK receptors, the two tissues show some similarities. Both pancreas and brain receptors show greater sensitivity to sulfated than to desulfated COOH-terminal octapeptide of CCK and display dissociation constants of 0.3-9.5 nM. The pancreas possesses about 300 times more binding sites than does brain. CCK binding in both brain and pancreas is enhanced by divalent cations and reduced by monovalent cations. Receptor binding in both tissues is regulated in a selective fashion by guanyl nucleotides.

Amino Acid Sequence↗
PubMed1979

Tricyclic antidepressant radioreceptor assay.

A radioreceptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-quinuclidinyl benzilate (3H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that in can detect, for example, 2 ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects.

Animals↗
PubMed1979

Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

Cholecystokinin octapeptide-like (CCK-OP-like) immunoreactivity was localized in the rat brain by using the indirect immunofluorescence method. Specificity in immunohistochemical studies was demonstrated by the virtual elimination of staining with either preimmune sera or sera preadsorbed with CCK-OP and by the achievement of similar fluorescent patterns with two different primary anti-CCK-OP sera. CCK-OP-like fluorescence was localized in neuronal cell bodies, fibers, and varicose terminals. The most dense collections of CCK-OP cells occurred in the periaqueductal gray and in the dorsomedial hypothalamus. Substantial numbers of cells and fibers also were present in the medial/dorsal and perirhinal cortex; more limited groups of cells were found in the pyramidal layer of the hippocampus and in the dorsal raphe.

Animals↗
PubMed1979

Bradykinin-like immunoreactive neuronal systems localized histochemically in rat brain.

Bradykinin-like immunoreactive structures were localized in rat brain by the indirect immunofluorescence method. Specificity of staining was demonstrated by: (i) the absence of fluorescence when preimmune serum was used, (ii) the disappearance of fluorescence when sera were preadsorbed with bradykinin, and (iii) the presence of identical staining with two different antisera. Immunoreactive neuronal cells are observed only in the hypothalamus, with especially dense clusters overlying the periventricular and dorsomedial nuclei. Fibers and varicose processes are observed in the periaqueductal gray matter, hypothalamus, perirhinal and cingulate cortices, the ventral portion of caudate-putamen, and the lateral septal area.

Animals↗
PubMedDate not supplied

Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia.

The mechanisms which contribute to the actions of atypical antipsychotic drugs, such as clozapine and the putative atypical agents remoxipride and raclopride, are reviewed. Examination of available preclinical and clinical data leads to two hypotheses concerning the mode of action of atypical antipsychotic drugs. The first hypothesis is that antagonism of the dopamine D2 receptor is both necessary and sufficient for the atypical profile, but that interaction with subtypes of the D2 receptor differentiates typical from atypical antipsychotic drugs. The second hypothesis has been previously advanced, and suggests that a relatively high ratio of serotonin 5-HT2:dopamine D2 receptor antagonism may subserve the atypical profile. It seems likely that the atypical antipsychotic drug profile may be achieved in more than one way.

Antipsychotic Agents↗