Biomedical subjects

M M Dietl

Publications and source records attributed to M M Dietl.

22 records · Page 2Linked to original sources

PubMed1987

On the distribution of cholecystokinin receptor binding sites in the human brain: an autoradiographic study.

Cholecystokinin (CCK) binding sites were localized by in vitro autoradiography in human postmortem brain materials from 12 patients without reported neurological diseases using [125I]Bolton-Hunter CCK octapeptide (BHCCK-8) as a ligand. The pharmacological characteristics of BHCCK-8 binding to mounted tissue sections were comparable to those previously reported in the rat. CCK-8 being the most potent displacer, followed by caerulein, CCK-4, and gastrin I. The distribution of BHCCK-8 binding sites was heterogeneous. These sites were highly concentrated in a limited number of gray matter areas and nuclei. The highest binding densities were seen in the glomerular and external plexiform layers of the olfactory bulb. BHCCK-8 binding sites were also enriched in the neocortex, where they presented a laminar distribution with low levels in lamina I, moderate concentration in laminae II to IV, high density in lamina V, and low levels in lamina VI. A different laminar distribution was seen in the visual cortex, where a low receptor density was observed in lamina IV but higher density in laminae II and VI. In the basal ganglia the nucleus accumbens, caudatus, and the putamen presented moderate to high densities of binding sites, while the globus pallidus lacked sites of BHCCK-8 binding. In the limbic system the only area presenting moderate to high density was the amygdaloid complex, particularly in the granular nucleus, while most of the thalamic nuclei were extremely poor or lacked BHCCK-8 binding. The hippocampal formation showed low (CA1-3) to moderate (subiculum) densities. Midbrain areas generally disclosed very low levels of BHCCK-8 binding sites. The pontine gray and the nucleus reticularis tegmenti pontis showed a relatively high density of CCK-8 receptor specific binding. Moderate to very high densities were found in few nuclei of the lower brainstem and spinal cord as the inferior olives and their accessory nuclei, the arcuate nuclei, the striae medullares, the efferent (motor) nucleus of the vagus, and the substantia gelatinosa of the cervical and thoracic spinal cord. These results are discussed in relation to the distribution of endogenous peptide and to the known physiological and pharmacological effects of substances acting on these receptors.

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PubMed1987

Autoradiographic mapping of [mono[125I]iodo-Tyr10, MetO17]vasoactive intestinal peptide binding sites in the rat brain.

The distribution of vasoactive intestinal peptide binding sites in the rat brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of vasoactive intestinal peptide (M-[125I]VIP) previously shown to maintain in the central nervous system the full biological activity of native vasoactive intestinal peptide was used for this study. In initial kinetic and pharmacological experiments the binding of M-[125I]vasoactive intestinal peptide to slide-mounted sections was shown to be time-dependent, saturable and reversible. Association of M-[125I]VIP specific binding was maximal within 90-120 minutes. Specific binding, corresponding to approximately 50% of total binding was saturable, of high affinity (Kd of 76.6 pM) and low capacity (fmol/mg prot range). Dissociation of M-[125I]VIP was maximal at 10 minutes. Unlabeled vasoactive intestinal peptide and the two structurally related peptides "peptide-histidine-isoleucine" (PHI) and secretin competed in a concentration-dependent manner for sites labeled by M-[125I]vasoactive intestinal peptide with the following rank order of potencies: vasoactive intestinal peptide greater than PHI greater than secretin. Vasoactive intestinal peptide receptors, as revealed by quantitative autoradiography, are present at various levels of the neuraxis. High densities were observed in olfactory bulb, cerebral cortex (highest in layers I, II, IV and VI), dentate gyrus, subiculum, various thalamic and hypothalamic nuclei, superior colliculus, locus coeruleus, area postrema, subependymal layer and pineal gland. Intermediate densities were found in the amygdala, nucleus accumbens, caudate-putamen, septum, bed nucleus of the stria terminalis, CA1 to CA4 fields of the hippocampus and central gray. No specific binding of M-[125I]vasoactive intestinal peptide was observed in white matter tracts such as corpus callosum, anterior commissure, medial forebrain bundle and fornix. The mapping of M-[125I]vasoactive intestinal peptide binding sites as revealed by autoradiography on slide-mounted sections indicates an association, although not exclusive, of vasoactive intestinal peptide receptors with brain regions involved in the processing of specific sensory inputs.

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PubMedDate not supplied

Mapping of benzodiazepine-like immunoreactivity in the rat brain as revealed by a monoclonal antibody to benzodiazepines.

A monoclonal antibody against benzodiazepines (21-7F9) was used to study the distribution of benzodiazepine-like immunoreactivity in the rat brain. Immunodensitometry in combination with image analysis were used for quantification. The results showed a ubiquitous distribution of benzodiazepine-like immunoreactivity throughout the brain. Very high levels of benzodiazepine-like immunoreactivity were found in the Purkinje cell layer of the cerebellum, in the primary olfactory cortex, in the stratum pyramidale of the hippocampus and in the mitral cell layer of the olfactory bulb. High densities of benzodiazepine-like immunoreactivity were found in the granule cell layer of the cerebellum, the pyramidal cell layer of the olfactory tubercle, the granule layer of the dentate gyrus, the arcuate nucleus of the hypothalamus, the mammillary bodies, the interstitial nucleus of Cajal and superficial grey layer of superior colliculus. The substantia nigra pars compacta, the islands of Calleja and layers II, III, V and VI of the cerebral cortex had moderate levels of benzodiazepine-like immunoreactivity. Lower densities were found in the internal granular layer and the external plexiform layer of the olfactory bulb, in the molecular layer of the dentate gyrus, in layers I and IV of the cerebral cortex, in the nucleus caudate-putamen and most of the thalamic nuclei. The lowest density of immunoreactivity was found in the globus pallidus, and the strata radiatum, oriens and lacunosum-moleculare of the hippocampus. The distribution of endogenous benzodiazepine-like immunoreactivity was compared with the distribution of the GABA/benzodiazepine receptor by using both immunocytochemistry and receptor autoradiography. Our studies have shown a clear mismatch between the localization of the benzodiazepine-like immunoreactivity and the GABA/benzodiazepine receptors.

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PubMedDate not supplied

The distribution of cholecystokinin receptors in the vertebrate brain: species differences studied by receptor autoradiography.

The regional distribution of cholecystokinin receptors in the brain of several vertebrate species including pigeon, rat, mouse, guinea-pig, cat, monkey and human was studied by in vitro auto-radiography using [125I] Bolton-Hunter cholecystokinin-octapeptide as a ligand. Cholecystokinin receptors presented marked species differences in several brain regions particularly in the laminar distribution of the cerebellar and cortical layers, in the hippocampal formation and in the basal ganglia. No binding was observed in the cerebellum of pigeon and rat, while intermediate to high densities of binding was observed in the cerebellum of the other species studied. In the pigeon external striatum, corresponding to the mammalian neocortex, low densities of cholecystokinin binding sites were observed. In contrast, mammalian neocortex was rich in cholecystokinin binding sites. However, the lamination was different from species to species, with high densities predominating in lamina IV in rat, mouse and guinea-pig cortex, in lamina II and VI in cat and monkey cortex and in lamina V in human cortex. Another area presenting important species differences was the hippocampal formation. The pigeon hippocampus showed intermediate densities of cholecystokinin receptors. In the mammals studied, very different patterns and densities of cholecystokinin binding sites were observed in the hippocampal formation. The basal ganglia were labelled in all species examined except the mouse. While biochemical and pharmacoganglia were labelled in all species examined except the mouse. While biochemical and pharmacological studies have shown that cholecystokinin receptors in different species present comparable characteristics, our autoradiographic investigations indicate that cholecystokinin binding sites are expressed differentially in several brain regions of different vertebrate species. The present autoradiographic study provides a morphological basis for further analysis on the expression and functionality of cholecystokinin receptors.

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