Biomedical subjects

L Grondin

Publications and source records attributed to L Grondin.

26 records · Page 2Linked to original sources

PubMed1987

Adrenergic receptor and catecholamine distribution in rat cerebral cortex: binding studies with [3H]prazosin, [3H]idazoxan and [3H]dihydroalprenolol.

The tritiated adrenergic antagonists [3H]dihydroalprenolol ([3H]DHA; beta-receptors), [3H]prazosin ([3H]PRZ; alpha 1-receptors), and [3H]idazoxan ([3H]IDA; alpha 2-receptors) were used to determine the distribution of these sites in 5 defined areas of the adult rat cerebral cortex. The highest density of [3H]PRZ binding was found in the prefrontal cortex, with a lower and homogeneous distribution for the frontal, parietal, occipital and temporal areas. The [3H]IDA binding sites were fairly uniform for all areas, except for the temporal cortex where it was very dense. In contrast, beta-adrenoceptors labelled by [3H]DHA were very homogeneous for all the regions examined. The functional significance of the distribution of alpha 1, alpha 2 and beta-adrenoceptors is discussed in relation to the catecholamine innervation and monoamine contents measured by high performance liquid chromatography.

Alprenolol↗

PubMed1987

Distribution of catecholamines, serotonin, and their major metabolites in the rat cingulate, piriform-entorhinal, somatosensory, and visual cortex: a biochemical survey using high-performance liquid chromatography.

The catecholamines noradrenaline (NA), dopamine (DA), adrenaline (AD), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, in four well-defined areas of the rat cerebral cortex: anterior cingulate (CIN;Cg1 and Cg3), piriform and entorhinal (PiEn), hind-limb primary somatosensory (SSC;HL) and primary visual (VIS; Oc1M and Oc1B). The concentrations of NA and that of its main metabolite 3-methoxy-4-hydroxyphenylglycol were highest in PiEn, had intermediate values in CIN and were lowest for SSC and VIS cortices. The DA levels were also highest in PiEn, intermediate in CIN, while the lowest values were in SSC and VIS cortices. The different DA/NA ratios support the hypothesis that they are indeed independent neurotransmitters. In addition, the levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine paralleled the distribution of DA, thus confirming the presence of release sites, even in regions in which the low levels of this catecholamine could be interpreted simply as the precursor of NA. Traces of AD were detected in all the regions examined. The 5-HT contents, as well as that of its precursor 5-hydroxy-1-tryptophan and that of its metabolite 5-hydroxyindole-3-acetic acid were also found to be non-homogenous, with the highest levels measured in the PiEn and CIN regions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: competition studies with [3H]prazosin and [3H]idazoxan.

The tritiated adrenergic antagonists prazosin ([3H]PRZ) and idazoxan ([3H]IDA, or RX-781094) bind specifically and with high affinity in membrane preparations from cerebral cortex to alpha-1- and alpha-2-adrenoceptors respectively. Saturation experiments, performed to determine the density of receptors (Bmax; maximum binding capacity) and the dissociation constant (Kd 25 degrees C), were analyzed by the methods of Eadie and Hofstee, iterative modelling, and the procedure of Hill. The pharmacologic properties and specificity of the labelling was verified by displacement experiments using alpha-adrenergic antagonists and agonists. The antagonist drugs showed the following order of potency to displace [3H]prazosin: prazosin much greater than phentolamine much greater than corynanthine greater than pyrextramine much greater than yohimbine much greater than piperoxan greater than benextramine greater than idazoxan; for the agonists: clonidine much greater than (-)-noradrenaline much greater than (-)-adrenaline much greater than phenylephrine, while other drugs, such as (-)-propranolol, dopamine, (-)-isoproterenol and serotonin only competed with the alpha-1-ligand at concentrations above 20 microM. The alpha 2-sites labelled by [3H]idazoxan were characterized by the antagonist displacement sequence idazoxan much greater than phentolamine greater than yohimbine = greater than piperoxan much greater than pyrextramine much greater than benextramine much greater than prazosin much greater than corynanthine. The agonists order of potency to compete with [3H]idazoxan was clonidine much greater than phenylephrine = greater than (-)-adrenaline greater than (-)-noradrenaline, and for other related drugs it was (-)-propranolol much greater than dopamine much greater than serotonin greater than (-)-isoproterenol. These competition experiments clearly showed two pharmacologically distinct sites, but question the relative specificity of some of the adrenergic drugs.

Adrenergic alpha-Agonists↗

PubMed1987

Stereospecific binding of a new benzazepine, [3H]SCH23390, in cortex and neostriatum.

The binding of the D1 antagonist SCH23390 to membrane preparations from rat cerebral cortex was examined using enantiomers of dopamine agonists and antagonists to compete with the bound [3H]SCH23390 at its Kd value. The competition curves were compared with those obtained with preparations from the neostriatum. The results demonstrate that specific [3H]SCH23390 binding in the cerebral cortex has the same pharmacological profile as in the neostriatum, so that this radioligand can be used to label dopamine D1 receptors in brain regions with a sparse dopaminergic innervation.

Animals↗

PubMed1986

Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: role of disulfide and sulfhydryl groups.

The tritiated adrenergic antagonists Prazosin ([3H]PRZ) and Idazoxan ([3H]IDA, or RX-781094) bind specifically and with high affinity to alpha 1 and alpha 2-adrenoceptors respectively, in membrane preparations from cerebral cortex. Saturation experiments performed to determine the density of receptors and the dissociation constant (Kd) were analyzed by the methods of Eadie Hofstee, iterative modelling, and the procedure of Hill, while the specificity of the labelling was verified by displacement experiments. Since receptors are proteins, we examined the role of disulfide (-SS-) bridges and sulfhydryl (-SH) groups in the specific combination of [3H]PRZ and [3H]IDA to the alpha 1 and alpha 2 adrenoceptors. Pretreatment of the membranes with the -SS- reactive DL-dithiothreitol (DTT) or the alkylating agent N-ethylmaleimide (NEM), alone or in combination, decreased specific binding of both ligands, with only minor changes in the non-specific counts. The [3H]IDA binding (alpha 2-sites) was more sensitive to both DTT and NEM than the [3H]PRZ sites (alpha 1-adrenoceptors), and the initial changes induced by alkylation of the alpha 2-site were due to an important decrease in the affinity for [3H]IDA, as judged by the increase in the Kd. This modulation in the affinity caused by alkylation of a thiol group could explain the higher potency of the blocking agent tetramine disulfide benextramine at the alpha 2-site. The results provide evidence for the participation of -SS- and -SH groups in the binding site of alpha 1- and alpha 2-adrenoceptors in the cerebral cortex.

Adrenergic alpha-Agonists↗

PubMed1986

Effects of p-chlorophenylalanine on cortical monoamines and on the activity of noradrenergic neurons.

The catecholamines noradrenaline, dopamine, adrenaline, the indoleamine 5-hydroxy-tryptamine (5-HT; serotonin), and some of their major metabolites were assayed, using high performance liquid chromatography (HPLC), in the neocortex of normal rats as well as in animals in which 5-HT synthesis had been inhibited with p-chlorophenylalanine. Besides important depletions in serotonin and in 5-hydroxyindole-3-acetic acid, noradrenaline levels were significantly reduced, but the content in 3-methoxy-4-hydroxyphenylglycol was increased, indicating an augmented utilization of this amine. The levels of dopamine and 3-methoxytyramine were also reduced, although homovanillic acid and 3,4-dihydroxyphenylacetic acid levels remained constant. The spontaneous unitary activity of identified noradrenergic neurons in the Locus coeruleus was increased, indicating an hyperactivity of this system. These results can be interpreted in relation to functional interactions between the catecholamines and serotonin; i.e.: a decrease in endogenous serotonin results in the loss of a negative feedback control of noradrenaline release.

Adrenergic Fibers↗

PubMed1986

Alpha-adrenoceptors and monoamine contents in the cerebral cortex of the rodent Jaculus orientalis: effects of acute cold exposure.

The tritiated adrenergic antagonists prazosin ([3H]PRZ) and idazoxan ([3H]IDA, or RX-781094) bind specifically and with high affinity to alpha 1- and alpha 2-adrenoceptors respectively, and were used to measure adrenoceptors in membrane preparations obtained from the cerebral cortex of Jaculus orientalis. Membrane preparations were also obtained from a group of cold exposed animals, to determine whether these adrenoceptors could be modified by a thermic stress. The density of receptors (Bmax; maximum binding capacity) and the dissociation constant (Kd 25 degrees C) were estimated by iterative modelling, and by using the procedure of Hill. After acute cold exposure (16 hr, 5 degrees C) there was a decrease in the affinity of the alpha 1-adrenoceptors, as judged by the Kd 25 degrees C for [3H]PRZ, with no changes in the Bmax. The alpha 2-sites did not show any significant changes, as revealed by [3H]IDA binding. Pretreatment of the membrane preparations from control animals with the disulfide and sulfhydryl reactives DL-dithiothreitol, 5,5'-dithiobis-(2-nitrobenzoic acid) and N-ethylmaleimide decreased specific [3H]PRZ and [3H]IDA binding, with minor changes in non-specific counts, indicating that the fixation of these ligands was to the receptor proteins. The endogenous cortical monoamine contents were also determined in the frontal cerebral cortex of these same animals, using high performance liquid chromatography with electrochemical detection. The catecholamine levels and their major metabolites were found to be stable in the cortex after the acute thermic stress, but there was a marked reduction in serotonin with a normal content in 5-hydroxyindole-3-acetic acid.

Animals↗

PubMedDate not supplied

[Venous physiology].

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Biological Transport↗