Biomedical subjects

L C Murrin

Publications and source records attributed to L C Murrin.

At least 19 recordsLinked to original sources

PubMed2005

Development of the norepinephrine transporter in the rat CNS.

The norepinephrine transporter (NET) plays a major role in regulating the actions of norepinephrine by removing norepinephrine from the synapse. Many studies suggest norepinephrine plays an important role in regulating development of the CNS, pointing to NET as an important factor in this process. We examined the ontogeny of NET expression in rat brain at 5, 10, 15, 20 and 25 days postnatally (PND) and in adults, using quantitative autoradiography with [3H]nisoxetine as ligand. At PND 5 and 10 most forebrain areas had low NET expression (1-2 fmol/mg tissue). By PND 15 most forebrain areas increased NET expression approximately five-fold compared with PND 10, levels generally similar to those found in the adult brain. In contrast, NET development in the brainstem exhibited elevated densities at PND 5, 10 and 20 that decreased in the adult. The locus coeruleus, in particular, had very high NET expression in the early postnatal period that decreased dramatically in the adult brain. These data illustrate a dynamic ontogenic profile for NET, characterized by developmental increases in forebrain structures and contrasting decreases in the brainstem. The early postnatal expression of NET in brainstem and the subsequent decrease or loss of NET expression with maturation suggest an important role for this transporter and for norepinephrine in the development of many brain regions. These studies also have important implications for use of drugs targeting the noradrenergic system in children and adolescents, such as antidepressants and drugs of abuse.

Animals↗

PubMed2004

Alpha-2 adrenergic receptor development in rat CNS: an autoradiographic study.

During development norepinephrine plays a role in determining the morphologic organization of the CNS and the density and future responsiveness of adrenergic receptors. alpha-2 Adrenergic receptors, one of three adrenergic receptor types, regulate important adult CNS functions and may have a distinct role during development. We examined alpha-2 receptor distribution and density in the rat brain at postnatal days 1, 5, 10, 15, 21, 28 and in adults using the antagonist [(3)H]RX821002 for autoradiography. Binding kinetics and pharmacology for alpha-2 adrenergic receptors were the same in adults and neonates. There was an overall increase in alpha-2 receptor levels during postnatal development with great variability in pattern and timing of receptor density changes among brain regions. Three major patterns were apparent. First, in many regions receptor density increased during postnatal development, generally reaching adult levels around postnatal day 15. Within this group there was variability in timing between regions and there were several regions with receptor densities higher than adult levels during the postnatal period. Second, there were regions with very high levels of receptors at birth and little or no change in density during the postnatal period. Third, some regions demonstrated decreasing or transient expression of alpha-2 adrenergic receptors in the course of postnatal development, including white matter regions, cerebellum and many brainstem nuclei, suggesting specific roles for alpha-2 receptors during development. This study investigates the development of alpha-2 adrenergic receptors in the rat CNS. It demonstrates there is region-specific regulation of alpha-2 receptor development and identifies brain regions where these receptors may play a specific and critical role in the regulation normal development.

Animals↗

PubMed2001

Agonist-stimulated [35S]GTPgammaS autoradiography: optimization for high sensitivity.

The receptor-stimulated accumulation of [35S]GTPgammaS provides a measure of functional coupling of G proteins with receptors. Sensitivity for autoradiographic visualization of [35S]GTPgammaS binding was improved two- to threefold in rat brain sections by optimizing assay conditions. Non-specific (NSB), basal and agonist-stimulated [35S]GTPgammaS binding were measured, using methadone, 5-carboxamidotryptamine and epinephrine for mu-opiate receptors, 5-HT(1A) receptors and alpha(2)-adrenoceptors. Basal and NSB were low in glycylglycine buffer compared to Tris or HEPES buffers, and agonist-stimulated [35S]GTPgammaS binding was more easily observed. Further optimization using glycylglycine buffer found increased signal-to-noise ratio with inclusion of dithiothrietol, increased [35S]GTPgammaS incubation time (2-4 h) and guanosine 5'-diphosphate (GDP) preincubation (20-30 min), and use of [35S]GTPgammaS at 0.1 nM. Improved sensitivity was due to decreased NSB and basal [35S]GTPgammaS binding and agonist-stimulated binding were similarly affected for each receptor system. The assay conditions described should extend the use of agonist-stimulated [35S]GTPgammaS autoradiography to receptors, which produce low levels of [35S]GTPgammaS binding and to the measurement of changes in receptor-G protein coupling.

Adrenergic Agonists↗

PubMed2001

A robust GTP-induced shift in alpha(2)-adrenoceptor agonist affinity in tissue sections from rat brain.

A method is presented for monitoring the coupling of the alpha(2)-adrenoceptor, as well as other receptors, to their G proteins using the GTP-induced shift in agonist affinity states. In tissue sections GTP, but not ATP, induces a robust decrease in agonist affinity of greater than 100-fold, which is much larger than previously found in membrane preparations. A sensitive and easy procedure to monitor the extent of coupling is to compare the amount of [(3)H]RX821002 binding remaining in the presence of 100 nM brimonidine in the absence and presence of 100 microM GTP. This method should be especially applicable for determining the extent of coupling of receptors to their G proteins in multiple brain regions using autoradiographic procedures.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2000

Radioligand saturation binding experiments over large concentration ranges.

Receptor analysis using the radioligand binding saturation method in situations requiring a large concentration range of the ligand is theoretically straightforward but in practice can be relatively difficult. In this paper we review three approaches for carrying out such experiments and assess the strengths and weaknesses of each. The three are two saturation experiments, two homologous competition experiments, and the mixed homologous saturation experiment. The best approach depends upon the experimental conditions and constraints of the system studied, but in general the mixed homologous saturation experiment appears to be the most effective at minimizing the amount of radioligand needed while providing the greatest reliability in the results.

Animals↗

PubMed2000

Alpha(2)-adrenoceptor-stimulated GTP gamma S binding in rat brain: an autoradiographic study.

Agonist-stimulated [35S]GTP gamma S binding by alpha(2)-adrenoceptors was examined in rat brain by autoradiography. Epinephrine, norepinephrine, dexmedetomidine and brimonidine stimulated [35S]GTP gamma S binding in a dose-dependent manner. Agonist-stimulated binding was blocked by the specific alpha(2)-adrenoceptor antagonist (1, 4-benzodioxan-2-methoxy-2-yl)-2-imidazoline hydrochloride (RX821002). Each alpha(2)-adrenoceptor agonist stimulated [35S]GTP gamma S binding in the same brain regions, corresponding to alpha(2)-adrenoceptor distribution determined by [125I]para-iodoclonidine autoradiography. The order of antagonist potency (RX821002>idazoxan>rauwolscine>phentolamine>prazosin), and weak inhibition by propranolol and selective serotonin antagonists, indicate that epinephrine-stimulated [35S]GTP gamma S binding is mediated primarily by alpha(2)-adrenoceptors. Several antagonists increased [35S]GTP gamma S binding at very high concentrations, and this effect had anatomic and pharmacologic characteristics of binding mediated by 5-HT(1A) receptors. These studies demonstrate functional linkage of alpha(2)-adrenoceptors to G proteins in tissue sections, thus providing data on neuroanatomic localization and a means to examine drug specificity at alpha(2)-adrenoceptors in different brain regions.

Animals↗

PubMed2000

Inverse agonism at alpha(2)-adrenoceptors in native tissue.

Several alpha(2)-adrenoceptor antagonists have inverse agonist properties in cell culture systems, usually expressing high levels or a constitutively active form of alpha(2)-adrenoceptors. In characterizing the binding of alpha(2)-adrenoceptor agonists to rat brain tissue sections, we found that conditions known to alter agonist affinity for these receptors, particularly the addition of 100 microM GTP, altered the binding of the alpha(2)-adrenoceptor antagonist, [3H](1,4-benzodioxan-2-methoxy-2-yl)-2-imidazoline hydrochloride (RX821002). In further studies, we found that under our conditions [3H]RX821002 demonstrates inverse agonist properties at alpha(2)-adrenoceptors. This is the first demonstration of inverse agonism at alpha(2)-adrenoceptors in native tissue. We found that the alpha(2)-adrenoceptor antagonist, (2S,12bS)1', 3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo(b)fu ro(2, 3-a)quinazoline)-2,4'-pyrimidin-2'-one (MK-912), did not have clearly discernible inverse agonist properties and acted as a neutral antagonist in these studies. On the other hand, the antagonist rauwolscine actually displayed partial agonist properties in our studies. These findings indicate that the inverse agonist properties of alpha(2)-adrenoceptor antagonists can be demonstrated in native tissue, as well as in tissue culture, and they strengthen the idea that inverse agonist properties may be of physiological and pharmacological importance.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2000

In vivo gene modification elucidates subtype-specific functions of alpha(2)-adrenergic receptors.

Mice with altered alpha(2)-adrenergic receptor genes have become important tools in elucidating the subtype-specific functions of the three alpha(2)-adrenergic receptor subtypes because of the lack of sufficiently subtype-selective pharmacological agents. Mice with a deletion (knockout) of the alpha(2A)-, alpha(2B)-, or alpha(2C)-gene as well as a point mutation of the alpha(2A)-gene (alpha(2A)-D79N) and a 3-fold overexpression of the alpha(2C)-gene have been generated. Studies with these mice indicate that most of the classical functions mediated by the alpha(2)-adrenergic receptor, such as hypotension, sedation, analgesia, hypothermia, and anesthetic-sparing effect, are mediated primarily by the alpha(2A)-subtype. The alpha(2B)-subtype is the principal mediator of the hypertensive response to alpha(2)-agonists, appears to play a role in salt-induced hypertension, and may be important in developmental processes. The alpha(2C)-subtype appears to be involved in many central nervous system processes such as the startle reflex, stress response, and locomotion. Both the alpha(2A)- and alpha(2C)-subtypes are important in the presynaptic inhibition of norepinephrine release and appear to have distinct regulatory roles. The ability to study subtype-specific functions in different mouse strains by altering the same alpha(2)-adrenergic receptor in different ways strengthens the conclusions drawn from these studies. Although these genetic approaches have limitations, they have significantly increased our understanding of the functions of alpha(2)-adrenergic receptor subtypes.

Adrenergic alpha-Agonists↗

PubMed1999

Alpha-2 adrenergic receptor functional coupling to G proteins in rat brain during postnatal development.

During postnatal development, alpha-2 adrenergic receptors (A2AR) change in both density and distribution. In forebrain, receptor density increases about 4-fold over neonatal levels, reaching adult levels before postnatal day (P) 28, whereas in hindbrain, including cerebellum, there is a decrease in overall receptor density. We examined the coupling of A2AR to G proteins using agonist-stimulated [35S]GTPgammaS binding as a functional assay. In forebrain the A2AR agonist-stimulated [35S]GTPgammaS binding increases rapidly after P7, reaching its highest levels at P21 and then declining slightly to adult levels. This binding increases more slowly than receptor number, suggesting that the appearance of G proteins, rather than the A2AR, determines the developmental appearance of functional A2AR-G protein interactions in forebrain. Basal [35S]GTPgammaS binding and [35S]GTPgammaS binding stimulated by other neurotransmitter receptor systems (GABA-B, mu opiate, and muscarinic) increase with a time course similar to A2AR-stimulated [35S]GTPgammaS binding. In contrast, in hindbrain, A2AR-stimulated [35S]GTPgammaS binding decreases during postnatal development in parallel with the decrease in A2AR levels, whereas [35S]GTPgammaS binding stimulated by other neurotransmitter receptor systems increases in parallel with basal [35S]GTPgammaS binding. Functional receptor-G protein coupling in hindbrain appears to be dependent on the developmental appearance of G proteins for most neurotransmitter systems. However, for A2AR the decrease in receptor density is the overriding factor. These studies 1) demonstrate the functional measurement of A2AR-G protein coupling in native tissue for the first time, 2) demonstrate that A2AR are coupled to G proteins throughout postnatal development, and 3) describe developmental increases and decreases in functional A2AR in brain.

Age Factors↗

PubMed1997

Dopamine transporter development in postnatal rat striatum: an autoradiographic study with [3H]WIN 35,428.

The dopamine transporter mediates the reinforcing effects of cocaine, thus playing a central role in human cocaine addiction, and perhaps providing the mechanism for inducing the effects of prenatal cocaine exposure. This possibility has stimulated growing interest in the normal and abnormal development of this transporter. [3H]WIN 35,428 is a cocaine analog that is useful for studying the distribution and density of the dopamine transporter in striatum and other brain regions. The postnatal development of the dopamine transporter in the rat striatum was measured by quantitative autoradiography with [3H]WIN 35,428. Dopamine transporter levels were low at birth, increased through day 15, followed by much more rapid growth in late postnatal development. The majority of the transporter sites appeared after day 15. Lateral to medial and anterior to posterior gradients in transporter density were established early during development, and there was also an early concentration of transporter in striosomes that became difficult to identify by day 15. Differences between the developmental patterns described here and studies using other ligands for the dopamine transporter suggest there are significant differences in the transporter binding sites for these drugs. These differences in transporter ligand binding characteristics may reflect developmental changes in post-translational modification of the transporter and/or changes in the functional activity rather than simply the presence of the transporter.

Animals↗

PubMed1996

Postnatal development of the dopamine transporter: a quantitative autoradiographic study.

The dopamine transporter performs an important role in regulating neurochemical transmission at dopaminergic synapses, as well as dopamine synthetic activity in dopaminergic neurons. Certain drugs and toxins exert effects at the transporter, especially cocaine, a common drug of abuse. We studied the development of these sites in the rat at postnatal ages day 0, 5, 10, 15, 21 and adult using quantitative autoradiography with the cocaine analogue [125I]RTI-55. At birth, certain structures such as the substantia nigra, interstitial nucleus of the medial longitudinal fasciculus, frontal and parietal cortex, and substantia inominata had [125I]RTI-55 binding levels that were already near the adult value. The striatum developed later, showing earlier growth in the anterior and dorsolateral regions, with early localization in both striosomes and a subcallosal streak. Anterior-to-posterior and lateral-to-medial gradients were present at day 0. The anterior striatum, ventral tegmental region, substantia nigra compacta and bed nucleus of the stria terminal is showed transient peaks in binding levels that were higher than the adult values. Structures showing relatively late development included the prefrontal cortex, nucleus accumbens shell, olfactory tubercle and subthalamic nucleus. Knowledge of the differential developmental patterns of the dopamine transporter in different brain regions may have implications for understanding the neurodevelopmental effects of prenatal cocaine exposure.

Animals↗

PubMed1996

17 beta-Estradiol inhibits the production of dopamine by the tuberoinfundibular dopaminergic neurons of the male rat.

Previous work in our laboratory suggests that the indirect stimulation of prolactin gene transcription observed in male rats between 3 and 6 h following estrogen injection results from an inhibition of dopamine release from the tuberoinfundibular dopaminergic neurons. To evaluate further the role of dopamine in the regulation of prolactin gene transcription by estrogens, we have examined the acute effects of 17 beta-estradiol (E2) on dihydroxyphenylalanine accumulation in the arcuate median eminence region and the amount of dopamine associated with the arcuate median eminence region. Dihydroxyphenylalanine accumulation in the arcuate median eminence region was unaffected when examined 2 h following a single injection of E2 (10 micrograms), and was reduced by 60% when examined 4 h following E2 treatment. When examined 4 h after E2 injection, dopamine content in the arcuate median eminence region was significantly increased. These data suggest that estrogens exert acute inhibitory effects on the tuberoinfundibular dopaminergic neurons of the male rat, and further support the assertion that the indirect stimulatory actions of estrogens on prolactin gene transcription result from inhibition of hypothalamic dopamine production.

Animals↗

PubMed1996

6-Hydroxydopamine-mediated induction of rat brain metallothionein I mRNA.

Oxidative stress, resulting either from excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in Parkinson's disease. Since metallothionein is able to regulate the intracellular redox potential, we have undertaken a group of experiments to learn whether or not 6-hydroxydopamine, which generates free radicals and is toxic to dopaminergic neurons, could alter the levels of zinc and metallothionein in the brain. The lesioning of the rat striatum with 6-hydroxydopamine (8.0 micrograms in 4 microliter 0.02% ascorbic acid) resulted in a reduction in the levels of zinc and metallothionein in the striatum but not other brain regions tested. However, the intracerebroventricular administration of 6-hydroxydopamine, in a dosage regimen that does not lesion catecholaminergic pathways but causes oxidative stress, enhanced dramatically the level of metallothionein I mRNA in some brain areas such as hippocampus, arcuate nucleus, choroid plexus, and granular layer of cerebellum, but not in the caudate putamen. The results of these studies are interpreted to suggest that zinc or metallothionein are altered in conditions where oxidative stress has taken place. Moreover, it is proposed that areas of brain, such as striatum containing high concentrations of iron, but low levels of inducible metallothionein are particularly vulnerable to oxidative stress.

Animals↗

PubMed1995

Localization and quantification of the dopamine transporter: comparison of [3H]WIN 35,428 and [125I]RTI-55.

Transport into the presynaptic terminal by the dopamine transporter is the primary mechanism for removing dopamine from the synaptic cleft. This transporter is a specific marker for dopamine terminals and is a primary site for CNS actions of cocaine. Several radioligands have been developed for analysis of the dopamine transporter. The ligands vary in affinity and specificity, leading to differences in reported transporter density in brain regions. We compared two of the most commonly used ligands, [3H]WIN 35,428 and [125I]RTI-55, analyzing the localization and density of sites in the rat brain using serial sections and quantitative autoradiography. Citalopram at 50 nmol/l was used to block [125I]RTI-55 binding to serotonin transport sites. Transporter density was highest in the striatum and both ligands labeled equivalent numbers of sites, with lateral to medial and anterior to posterior gradients. In most areas the density of sites measured with the two ligands was similar. However, [125I]RTI-55 binding was significantly higher than [3H]WIN 35,428 binding in the substantia nigra zona compacta, ventral tegmental area, subthalamic nucleus and a number of other subcortical nuclear groups while [3H]WIN 35,428 binding was higher in lateral striatum and in olfactory tubercle. These differences could reflect different forms of the transporter, perhaps due to post-translational modifications, and they may provide a basis for differential pharmacological regulation of transporter function in discrete brain regions and disease states.

Animals↗

PubMed1995

In situ hybridization analysis of CHOT1, a creatine transporter, in the rat central nervous system.

A putative choline transporter (CHOT1) has been cloned from rat brain and is reported to express a high-affinity, sodium-dependent, hemicholinium-3-insensitive choline transporter in oocytes. A second transporter (OCCREATRA) cloned from rabbit brain is 98% homologous to CHOT1 and is reported to transport creatine. We examined the distribution of CHOT1 mRNA in rat brain by in situ hybridization, using a 48 base oligonucleotide probe. In adult rats, the hybridization signal was widespread, but with a distinct pattern. High levels of expression were detected in the cerebellum (Purkinje and granule cell layers), choroid plexus, medial habenula, pontine nuclei, several brainstem nuclei, and hippocampus (pyramidal cell layer). Moderate signal was detected in cortex, globus pallidus, corpus callosum, and most other white matter tracts. Very low levels were present in striatum, nucleus accumbens, hippocampus molecular layer, and cerebellar molecular layer. Emulsion autoradiography indicated cellular localization to both neurons and glia. CHOT1 mRNA was relatively abundant in some cholinergic regions, including the medial habenula, the medial septum, and several brainstem nuclei. However, the overall pattern was distinctly different from that expected for cholinergic markers and correlated well with the localization of creatine kinase. The widespread distribution and poor correlation with cholinergic markers indicates that the CHOT1 gene does not encode the classical choline transporter known to be associated with acetylcholine synthesis. It is possible that CHOT1 is associated with cholinergic neurotransmission in some brain regions. However, it appears to encode that the rat creatine transporter, and its widespread and heterogeneous distribution suggests regions where creatine phosphate is an important energy source.

Animals↗

PubMed1995

Expression and regulation of brain metallothionein.

Many, but not all, zinc-containing neurons in the brain are a subclass of the glutamatergic neurons, and they are found predominantly in the telencephalon. These neurons store zinc in their presynaptic terminals and release it by a calcium-dependent mechanism. These "vesicular" pools of zinc are viewed as endogenous modulators of ligand- and voltage-gated ion channels. Metallothioneins (MTs) are low molecular weight zinc-binding proteins consisting of 25-30% cysteine, with no aromatic amino acids or disulfide bonds. The areas of the brain containing high contents of zinc such as the retina, the pineal gland, and the hippocampus synthesize unique isoforms of MT on a continuous basis. The four MT isoforms are thought to provide the neurons and glial elements with mechanisms to distribute, donate, and sequester zinc at presynaptic terminals; or buffer the excess zinc at synaptic junctions. In this cause, glutathione disulfide may participate in releasing zinc from MT. A similar nucleotide and amino acid sequence has made it difficult to obtain cDNA probes and antibodies capable of distinguishing indisputably among MT isoforms. MT-I and MT-II isoforms are found in the brain and in the peripheral tissues; MT-III isoform, possessing an additional seven amino acids, is expressed mostly in the brain and to a very minute extent in the intestine and pancreas; whereas MT-IV isoform is found in tissues containing stratified squamous epithelial cells. Since MTs are expressed in neurons that sequester zinc in their synaptic vesicles, the regulation of the expression of MT isoforms is extremely important in terms of maintaining the steady-state level of zinc and controlling redox potentials. The concentration of zinc has been shown to be altered in an extensive number of disorders of the central nervous system, including alcoholism. Alzheimer-type dementia, amyotrophic lateral sclerosis, Down's syndrome, epilepsy, Friedreich's ataxia, Guillaine-Barré syndrome, hepatic encephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, retinitis pigmentosa, retinal dystrophy, schizophrenia, and Wernicke-Korsakoff syndrome. The status of MT isoforms and other low molecular weight zinc-binding proteins in these conditions, diseases, disorders, or syndromes is being delineated at this time. Since several of these disorders, such as amyotrophic lateral sclerosis, are associated with oxidative stress, and since MT is able to prevent the formation of free radicals, it is believed that cytokine-induced induction of MT provides a long-lasting protection to avert oxidative damage.

Amino Acids↗

PubMed1994

Localization of nicotinic cholinergic receptors in rat brain: autoradiographic studies with [3H]cytisine.

There is a great deal of interest in the role of nicotinic acetylcholine receptors in the central nervous system, although their function is not well understood at present. Currently, central nicotinic receptors can be classified broadly as either alpha-bungarotoxin binding sites with low affinity for acetylcholine agonists, or as high-affinity agonist binding sites with low affinity for alpha-bungarotoxin. Neuronal nicotinic receptors with a high affinity for agonists are distributed widely in the central nervous system. Evidence from molecular biology and electrophysiology suggests that multiple nicotinic receptor types exist in the brain. In this study we have used the agonist [3H]cytisine as a ligand for autoradiography to generate a detailed quantitative map of the high-affinity agonist binding nicotinic receptor in the rat brain. Optimized binding conditions, characterization of the kinetic and equilibrium binding properties, and demonstration of the nicotinic pharmacology of this binding site in tissue sections confirm the usefulness of [3H]Cytisine as a ligand for nicotinic receptor autoradiography. [3H]Cytisine autoradiography provides excellent anatomic resolution with very low non-specific binding. This property has allowed us to describe variations in receptor density within subnuclei and gradients of receptor density in larger brain regions. Data from several studies suggest that the predominant high-affinity agonist binding nicotine receptor in the central nervous system is composed of the alpha 4 and beta 2 subunits. The data in the current study are consistent with the suggestion that [3H]cytisine labels only the alpha 4 beta 2 nicotinic receptor with high affinity, offering the possibility of localizing a specific nicotinic receptor subtype in the central nervous system. In summary, we characterize the optimum experimental conditions for the use of [3H]cytisine in tissue section autoradiography. [3H]Cytisine proves to be an excellent marker for nicotinic cholinergic receptors with a very high affinity and very low background. We provide a detailed quantitative characterization of nicotinic receptor density in the rat central nervous system and we find there are significant variations and gradients in receptor density within specific brain regions, including subregions previously thought to be homogeneous.

Alkaloids↗

PubMed1994

Distribution of cholinergic and dopaminergic receptors in rainbow trout pineal gland.

The involvement of multiple receptors in modulating the function of the pineal gland was investigated by searching for dopaminergic and cholinergic receptors in trout pineal gland. Dopamine D1 and D2 receptors were measured using [3H]SCH23390 and [3H]spiperone, respectively. Muscarinic and nicotinic cholinergic receptors were measured using quinuclidinyl benzilate ([3H]QNB) and [3H]methylcarbamyl choline, respectively. High-affinity choline uptake sites were measured using [3H]hemicholinium-3. The distribution of dopaminergic receptors varied throughout the pineal gland in that the density of D2 receptors, which was higher than that of D1 receptors, was most abundant in the distal region, exhibiting a value of 112 +/- 17 fmol/mg tissue. The distribution of both muscarinic and nicotinic receptors was uniform throughout the pineal gland. However, the highest value for the high-affinity choline transporter (106 +/- 17 fmol/mg tissue) occurred in the proximal portion of the trout pineal gland. The results of these studies indicate that the pineal gland should not be viewed as a homogeneous tissue possessing identical density of various receptors. Furthermore, these results, along with previous data, are interpreted to suggest that different regions of pineal gland may indeed possess unique functions.

Animals↗