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L C Murrin

Publications and source records attributed to L C Murrin.

At least 55 records · Page 3Linked to original sources
PubMed1986

Postnatal ontogeny of dopamine D2 receptors in rat striatum.

Studies of the ontogeny of dopamine D2 receptors in rat striatum were carried out using [3H]spiroperidol as ligand in the presence of 30 nM ketanserin. D2 receptors increased with age, and saturation studies indicated that this was due to an increase in receptor density (Bmax) and not to a change in affinity (KA). By 21 days of age, receptor density had reached adult levels. Hill plots indicated no cooperativity in the binding from 7 to 21 days of age. Pharmacologically, receptors at 7, 14 and 21 days of age were similar to those of adult rats, exhibiting characteristics of dopamine D2 receptors. These studies provide a basic analysis of dopamine D2 receptors in rat striatum during early postnatal development.

Age Factors↗
PubMed1986

Muscarine binding sites in bovine adrenal medulla.

The presence of muscarinic binding sites in the bovine adrenal medulla was investigated using [3H]QNB and the bovine adrenal medulla. Scatchard analysis combined with computer analysis yielded data consistent with a two binding site configuration. KDs of 0.15 and 14 nM and Bmax s of 29 and 210 fmol/mg protein, respectively, were observed. Displacement of [3H]QNB by various cholinergic agents is, in order of decreasing potency: QNB, dexetimide, atropine, scopolamine, imipramine, desipramine, oxotremorine, pilocarpine, acetylcholine, methacholine and carbachol. These results demonstrate the presence of more than one muscarine binding site in the bovine adrenal gland.

Adrenal Medulla↗
PubMed1986

Identification of a Cl-/Ca2+-dependent glutamate (quisqualate) binding site in bovine pineal organ.

The presence of a high concentration of glutamic acid, a transmitter shown to have excitatory action in the pineal organ, prompted us to search for and to characterize glutamate receptor site in the bovine pineal organ. By using 10 nM- 100 microM of labeled and unlabeled L-glutamate and by employing the LIGAND computer program, we found a glutamate binding site with a dissociation equilibrium constant (KD) of 0.534 microM and a receptor density (Bmax) of 4.84 pmol/mg protein. This pH- and temperature-dependent binding site showed stereospecificity, was activated by Ca2+, and displayed affinity for both glutamate agonists and antagonists. The IC50 values for L-glutamate, L-aspartate, L-cysteate, L-cysteine sulfinate, quisqualate, and (+/-) ibotenate were 0.5, 2, 12, 16, 25, and 30 microM, respectively, whereas those for D-aspartate, L-alpha-aminoadipate, L-homocysteate, and DL(+/-) 2-amino-4-phosphonobutyrate were greater than 100 microM. Kainate, N-methyl-D-aspartate, and L-glutamic acid diethyl ester were inactive. Based on these results, the presence of a quisqualate-type, Cl-/Ca2+-dependent glutamate binding site in the pineal organ is suggested, and a possible neuroexcitatory role for glutamic acid, aspartic acid, and certain sulfur-containing amino acids is also implied. The precise nature of this excitatory effect in modulating the function(s) of the pineal organ and the synthesis of its hormone(s) remains to be elucidated.

Animals↗
PubMed1986

Bromocriptine holiday: effects on dopamine receptors and turning behavior in rats.

In experimental Parkinson's disease, we studied the effects of chronic administration (30 days), withdrawal, and reinstitution of bromocriptine. Dopamine (DA) receptor supersensitivity was produced by 6-hydroxydopamine and reversed by chronic bromocriptine administration. Drug holiday reestablished sensitivity of DA receptors, but reinstitution of bromocriptine again downregulated receptors. The effects of a drug holiday on DA receptors are short-lived, and long-term clinical improvement cannot be expected. Apomorphine-induced contralateral turning produced by the lesion was unaffected by any drug regimen.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Ontogeny of dopamine, serotonin and spirodecanone receptors in rat forebrain--an autoradiographic study.

Sections from freshly frozen neonatal rat brain, ages 0-21 days, were incubated with [3H]spiperone (SP). Initial studies characterized the binding sites for SP in terms of association and dissociation rates, saturability and pharmacology. The binding sites were found to be predominantly dopamine D2 receptors in sections centered in the striatum and these receptors were similar to receptors in adult brain. Autoradiographic studies using in vitro techniques examined the anatomic distribution of [3H]SP binding sites. Using domperidone, ketanserin and (+)butaclamol it was possible to differentiate dopamine D2, serotonin S2 and spirodecanone receptors. Dopamine receptors were found at birth in striatum and nucleus accumbens and increased in density with age. In the first two weeks postnatally there was an apparent dorsolateral to ventromedial gradient in the striatum. Serotonin S2 receptors were found in the cortex, lateral olfactory tubercles and nucleus accumbens and claustrum. These receptors increased in density with age but to a much lesser extent than dopamine receptors. Spirodecanone receptors were first apparent in the piriform cortex by day 5. They became very dense with age in particular regions, i.e., layer II of cortex, piriform cortex, medial olfactory tubercles, lateral septum and in patches in the nucleus accumbens. These studies delineate with a high resolution at an anatomical level the major receptor sites for neuroleptic drugs in the developing rat forebrain. They describe the developmental pattern of these receptors and provide a basis for further studies on their control and function during development.

Animals↗
PubMed1985

Effects of L-dopa supplementation on concentrations of brain catechols, dopamine receptor binding and the incidence of pale, soft and exudative meat in stress-susceptible pigs.

The purpose of this research was to determine if chronic dietary L-DOPA supplementation will alter differentially the brain catechol concentrations, dopamine receptor binding (KD and Bmax) and the incidence of pale, soft and exudative (PSE) meat in stress-susceptible (SS) and stress-resistant (SR) pigs. Stress-susceptible and SR pigs were assigned randomly to these four groups: SS pigs as controls, SR pigs as controls, SS pigs with L-DOPA supplementation and SR pigs with L-DOPA supplementation. The experiment began when pigs weighed 23 kg and terminated when pigs weighed 95 kg. Anatomical brain structures removed at slaughter included hypothalamus, thalamus, cortex, cerebellum, olfactory bulb, caudate nucleus, putamen and substantia nigra. Concentrations of norepinephrine and dopamine were greater in the hypothalami of SS than of SR control pigs. The L-DOPA supplementation eliminated the strain differences of brain catecholamine concentrations. Pigs fed L-DOPA had greater concentrations of dihydroxyphenylacetic acid in six of the eight brain regions analyzed than the controls. Dopamine receptor binding (Bmax and KD) of spiroperidol was similar in all four groups of pigs. Pale, soft and exudative pork developed to the same extent in SS pigs with or without L-DOPA treatment. The results suggest that L-DOPA supplementation eliminates strain differences in brain catecholamine concentrations but does not alter PSE meat development or striatal dopamine receptor binding.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Ontogeny of the rat striatum: correspondence of dopamine terminals, opiate receptors and acetylcholinesterase.

The ontogeny of dopamine terminals, mu opiate receptors and acetylcholinesterase (AChE) in rat striatum were examined during the first two weeks postnatally using fluorescence histochemistry, autoradiography and AChE stain, respectively. The most dense regions of all three markers were superimposable, particularly in the dorsal third of the striatum, as long as the dense regions could be clearly visualized. This anatomic overlapping of markers for three neuronal systems suggests an important and distinct relationship between these neuronal systems during development in addition to that already seen in adult tissue.

Acetylcholinesterase↗
PubMed1984

Characterization of dopaminergic receptor sites in bovine pineal gland.

In addition to beta-adrenergic receptor agonists, L-dopa and dopamine have been also shown to activate the production of melatonin and its synthesizing enzyme, serotonin N-acetyltransferase. In an attempt to characterize dopaminergic receptor sites, bovine pineal synaptosomes were prepared by differential centrifugation techniques. Washed disrupted synaptic membranes were used to study 3H-spiroperidol binding, using standard membrane-binding techniques. Association of 3H-spiroperidol to pineal membranes was very rapid, reaching equilibrium within 2 min and remaining stable for 20 min. Dissociation was also rapid with a t 1/2 of 3 min. Analysis of saturation studies (0.035 to 20 nM spiroperidol, 16 concentrations) using the LIGAND program indicated the presence of two binding sites with KDS (dissociation equilibrium constant) of 0.18 nM and 2.1 nM. The Bmax's (receptor density) of the sites were 37 and 630 fmoles/mg protein respectively. The IC50S of haloperidol, cis-flupenthixol, and chlorpromazine were 8, 12, and 80 nM, respectively, while those of pipamperone, cyproheptadine, and cinanserin were 60, 400, and 1500 nM. These and other data indicate that the most abundant site is a dopamine D2 receptor while the less abundant site may be a serotonin receptor. The function of dopamine and dopaminergic neurons in bovine pineal gland is not known and has not been established.

Animals↗
PubMed1984

Dopamine receptors: effects of chronic L-dopa and bromocriptine treatment in an animal model of Parkinson's disease.

Male albino rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra. Animals demonstrating contralateral rotations 2 weeks postoperatively with apomorphine (0.5 mg/kg i.p.) were treated with L-Dopa (55 mg/kg i.p.), bromocriptine (2 mg/kg i.p.), or polyethylene glycol (vehicle) every 12 h for 30 days. Striatal dopamine (DA) receptors were analyzed by Scatchard plot using 3H-spiroperidol (3H-SP) as ligand. 3,4-Dihydroxyphenylacetic acid (DOPAC) and DA were measured by use of high pressure liquid chromatography. 6-OHDA lesions produced a supersensitivity in striatal DA receptors. Chronic L-Dopa or bromocriptine treatment reversed this supersensitivity. Neither lesion nor drug treatment alone or together produced a significant change in affinity (KD) for 3H-SP. Drug treatment alone also had no effect on Bmax. DA and DOPAC levels were reduced by greater than 98% in lesioned striata. Neither drug treatment affected DA or DOPAC levels as compared with controls. These results indicate that chronic administration of either bromocriptine or L-Dopa will reverse the DA receptor denervation supersensitivity in striatum seen following 6-OHDA lesion. This reversal may play a role in the clinical changes seen in Parkinson's disease patients following chronic use of these drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Characteristics of 3H-cis-flupenthixol binding in rat striatum.

Characteristics of membrane receptor binding by 3H-cis-flupenthixol were examined in rat striatum. Using modifications of standard dopamine receptor binding techniques, it was possible to obtain 70% specific binding with 3H-cis-flupenthixol. Association and dissociation rates were very rapid, with equilibrium reached in 2 min and half-time of dissociation being 1 min. Analysis of saturation and competition studies using cis-flupenthixol and spiroperidol indicated that cis-flupenthixol binds to two striatal receptors with apparent KD's of 0.7 and 4.8 nM. It is suggested these represent D1 and D2 dopamine receptors respectively. The further characterization of the properties of cis-flupenthixol binding presented here should enable more detailed studies of multiple dopamine receptors to be designed.

Animals↗
PubMed1983

Transport of histidine into synaptosomes of the rat central nervous system.

Histidine transport into synaptosomes was studied in order to characterize this aspect of histamine synthesis in neurons. Histidine transport was found to be independent of sodium, calcium, and magnesium ions and dependent upon potassium and chloride ions. Histidine transport was also found to be energy dependent, and fractionation studies suggested it was highly localized to nerve terminals. Kinetic analysis of histidine transport in several brain regions indicated the presence of two uptake sites, a high-affinity site with a Km of approximately 35 microM and a low-affinity site with a Km in the millimolar range. Density of the high-affinity site, as reflected by Vmax, correlates well with density of proposed histaminergic innervation. Rate of histidine transport was not altered by prior depolarization of the synaptosomes, indicating that histidine transport probably does not play a regulatory role in histamine synthesis.

2,4-Dinitrophenol↗
PubMed1982

In vivo studies of dopamine receptor ontogeny.

Studies of the ontogeny of dopamine and neuroleptic receptors in the central nervous system of the rat were carried out in vivo using 3H-spiperone as ligand. It was demonstrated that intraperitoneal injections can be successfully used to label these receptors in rat pups up to at least 30 days of age. The time course and characteristics of 3H-spiperone binding in the brain of 5, 15 and 30 day old rat pups were determined and found to include appropriate regional distribution, saturability and appropriate pharmacology. The developmental pattern of 3H-spiperone binding paralleled what has been seen using in vitro techniques. In addition preliminary autoradiographic studies describe the neuroanatomical pattern of dopamine receptor ontogeny in the striatum.

Aging↗
PubMed1979

Autoradiographic localization of neuroleptic and dopamine receptors in the caudate-putamen and substantia nigra: effects of lesions.

The localization of neuroleptic receptors was studied in the caudate-putamen (CP) and the zona compacta of the substantia nigra using light microscopic autoradiography of 3H-spiperone binding sites. Lesion of the dopaminergic input to the caudate-putamen produced an increase in receptors in the CP, possibly reflecting denervation supersensitivity. Kainic acid lesions and decortication produced significant decreases of 61% and 18% in striatal receptors. This suggests that in the caudate-putamen most of the dopamine receptors are on intrastriatal neurons, but some are also localized to the afferents from the cortex. Lesion of the nigro-striatal dopaminergic pathway produced a large (48%) decrease in receptor sites in the substantia nigra zona compacta while kainic acid intrastrially and striato-nigral pathway lesions had no significant effect. These results suggest that the majority of dopamine receptors in the zona compacta which bind neuroleptics are located on cell bodies and processes of dopaminergic neurons and are anatomically distinct from dopamine-stimulated adenylate cyclase sites.

Animals↗