Search PubMed⌕ Search

Biomedical subjects

L C Mahan

Publications and source records attributed to L C Mahan.

At least 19 recordsLinked to original sources
PubMed1997

Method for identifying ligands activating either excitatory or inhibitory G-protein-coupled receptors by functional coexpression in Xenopus oocytes.

Xenopus oocytes devoid of their follicular enclosure provide a frequently used expression system for investigating receptors that transduce through activation of adenylyl cyclase following injection of the appropriate mRNA. However, due to a low basal activity of the cyclase they cannot be utilized to investigate receptor-mediated reductions in endogenous cAMP levels. In order to overcome this limitation, a model was designed in which test clones for such inhibitory receptors were co-expressed with a beta 2-adrenoceptor, which elevated cAMP upon exposure to isoproterenol. Following injection of mRNA to express the alpha 2 test receptor in the oocytes, marked reduction in cAMP could be measured after exposure to clonidine. Attenuation of cAMP levels was also seen following co-expression of the dopamine D2 receptor along with dopamine administration. Thus, after inducing a receptor-mediated tone in adenylyl cyclase activity, Xenopus oocytes can be conveniently used to study also ligands that bind to inhibitory G-protein coupled receptors.

Adenylyl Cyclases↗
PubMed1997

Characterization of liposome-mediated gene delivery: expression, stability and pharmacokinetics of plasmid DNA.

We have characterized a new synthetic gene delivery system, termed DLS, which may be suitable for systemic gene therapy. DLS constitutes a lipopolyamine and a neutral lipid and associated plasmid DNA in the formation of lamellar vesicles (DLS-DNA). The ratio of lipids and lipid to DNA as well as the method of preparation were optimized to yield a high in vitro transfection efficiency compared with that previously reported for cationic lipid systems. DLS-DNA showed a rapid cellular uptake and distribution in the cytoplasmic and nuclear (especially in the nucleoli) compartments as determined by laser-assisted confocal microscopy. There was little or no plasmid DNA degradation over a period of 20 min, relatively slow plasma clearance, and effective and rapid cellular uptake of DLS-DNA following intravenous administration in mice. Supercoiled plasmid DNA could be detected in blood cells up to 1 h after injection. Systemic administration of DLS-DNA yielded transgene expression in mouse tissues, such as in lung or liver. The ratio of DLS:DNA and the procedure used to form DLS-DNA affected both the level and cellular specificity of expression of a luciferase reporter gene showing that in vitro transfection efficiency of DLS-DNA formulations cannot be easily extrapolated to an in vivo setting. Optimization of the formulation of a DNA delivery system was critical to obtain a defined structure resulting in a preparation with high reproducibility and stability, greater homogeneity of particle size and high efficacy following systemic gene transfer. In addition, the DLS system may be formulated for specific target tissues and may have a wide range of applications for gene therapy.

Animals↗
PubMed1996

GABAA receptors modulate early spontaneous excitatory activity in differentiating P19 neurons.

P19 embryonic carcinoma (EC) stem cells are pluripotent and are efficiently induced to differentiate into neurons and glia with retinoic acid (RA) treatment. Within 5 days, a substantial number of differentiating P19 cells express gene products that are characteristic of a neuronal phenotype. P19 neurons were used as a model to explore the relationship between neuronal "differentiation" in vitro and the acquisition of gamma-aminobutyric acid (GABAA) receptors and functional GABA responses. Pulse-labeling experiments using bromodeoxyuridine indicated that all neurons had become postmitotic within 3-4 days after treatment with RA. This was confirmed by a reduction in the immunocytochemical detection of the undifferentiated stem cell antigen SSEA-1. Subsequently, a transient expression of nestin was observed during the first 5 days in vitro (DIV) after exposure to RA. By 5-10 DIV after RA, a significant number of neurons (approximately 80-90%) expressed immunocytochemically detectable glutamate decarboxylase and GABA coincident with the acquisition of membrane binding sites for tetanus toxin. These phenotypic markers were maintained for > 30 DIV after RA. Under current-clamp conditions, random, low-amplitude, spontaneous electrical activity appeared in neurons within the first few days after RA treatment and this was blocked by the specific GABAA receptor antagonist bicuculline. Thereafter, the appearance and progressive increases in the frequency of spontaneous action potentials in P19 neurons were observed that were similarly attenuated by bicuculline. In neurons > 5 DIV after RA, exogenous application of GABA elicited similar action potentials. The onset of excitatory responses to GABA or muscimol in voltage-clamped neurons appeared immediately after the cessation of neuronal mitosis and before the previously reported acquisition of responses to glutamate. In fura-2 imaging studies, the exogenous application of GABA resulted in neuron-specific increases in intracellular Ca2+. Thus, P19 neurons provide an in vitro model for the study of the early acquisition and properties of electrical excitability to GABA and the expression of functional GABAA receptors.

Action Potentials↗
PubMed1995

Systemic gene therapy: biodistribution and long-term expression of a transgene in mice.

We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) with episomally replicative DNA plasmids to effect long-term expression of a transgene in cells. A single i.v. injection of a plasmid DNA vector containing the luciferase gene as a marker was administered with the DLS liposomes in BALB/c mice. The luciferase gene and its product were found in all mouse tissues tested as determined by PCR analysis and immunohistochemistry. Luciferase activity was also detected in all tissues tested and was present in lung, liver, spleen, and heart up to 3 months postinjection. In contrast to the nonepisomal vectors tested (pRSV-luc and pCMVintlux), human papovavirus (BKV)-derived episomal vectors showed long-term transgene expression. We found that these episomal vectors replicated extrachromosomally in lung 2 weeks postinjection. Results indicated that transgene expression in specific tissues depended on the promoter element used, DNA/liposome formulation, dose of DNA per injection, and route of administration.

Animals↗
PubMed1995

Extrapituitary expression of the rat V1b vasopressin receptor gene.

[Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned V1a and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the V1a and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.

Amino Acid Sequence↗
PubMed1993

Co-existent expression of GABAA receptor beta 2, beta 3 and gamma 2 subunit messenger RNAs during embryogenesis and early postnatal development of the rat central nervous system.

The expression of beta 1, beta 2, beta 3, gamma 2 and delta subunit messenger RNAs of the GABAA receptor was followed by in situ hybridization histochemistry using radiolabeled oligodeoxynucleotide probes in sections of embryonic (E12-21) and early postnatal (P1-5) rat. beta 2, beta 3 and gamma 2 subunit messenger RNAs were first detectable at E15 in the spinal cord (ventral > dorsal) and lower central nervous system regions (e.g. pons, medulla and thalamus). beta 3 subunit messenger RNA was abundantly expressed in olfactory bulb neurons at E15. At E17, the expression pattern of these subunit messenger RNAs continued in the lower central nervous system. In the upper central nervous system, beta 2, beta 3, and gamma 2 subunit messenger RNAs were first detectable in the outer layer of the hippocampal and entire cortical neuroepithelium. The expression for both beta 3 and gamma 2 subunit messenger RNAs increased significantly over that observed at E15, whereas beta 2 subunit messenger RNA increased to a lesser extent and was more discretely expressed in inferior colliculus, cerebellar neuroepithelium and spinal cord (ventral = dorsal). By E19, messenger RNAs for beta 2, beta 3 and gamma 2 subunits a widespread and abundant co-existent distribution throughout the central nervous system. Exceptions to this co-expression were the absence of beta 2 messenger RNA in the dentate gyrus and beta 3 messenger RNA in entorhinal cortex, areas in which they are present in adult. There was also a differential distribution of subunit messenger RNAs in developing olfactory bulb at E19-20: the glomerular cells preferentially expressed beta 3 and gamma 2 subunit messenger RNAs; the mitral cells preferentially expressed beta 2 subunit messenger RNA; inner granule cells expressed moderate levels of beta 2, beta 3 and gamma 2 subunit messenger RNAs. Expression of beta 2, beta 3 and gamma 2 messenger RNAs was also anatomically co-existent at P5. In addition, significant expression of beta 1 and delta subunit messenger RNAs was apparent in hippocampus and entorhinal cortex. The identity of the gamma 2 expressed between E15 and E21 was shown to be mostly the short isoform of gamma 2 subunit messenger RNA. Expression of both forms was evident beginning around P3-5. These results indicate that during the late embryonic and early postnatal period of development, beta 2, beta 3 and gamma 2 subunit messenger RNAs are abundantly expressed and co-localized to most central nervous system regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Characterization of a naturally occurring ecotropic receptor that does not facilitate entry of all ecotropic murine retroviruses.

A fibroblast cell line (MDTF) derived from the feral mouse Mus dunni is resistant to infection by Moloney murine leukemia virus (Mo-MuLV), an ecotropic murine leukemia virus (E-MuLV) (M. R. Lander and S. K. Chattopadadhyay, J. Virol. 52:695-698, 1984). MDTF cells can be infected by other E-MuLVs such as Friend MuLV and Rauscher MuLV, which have been demonstrated to use the same receptor as Mo-MuLV in NIH 3T3 cells (A. Rein and A. Schultz, Virology 136:144-152, 1984). We have now shown that the block to Mo-MuLV infection of MDTF cells occurs at the level of the envelope-receptor interaction. We have cloned the ecotropic receptor cDNA from MDTF cells (dRec) and compared its sequence with that of the NIH 3T3 cell receptor (mRec). Although the deduced dRec and mRec proteins differ at only four amino acid residues, we demonstrate that these changes account for the resistance of MDTF cells to Mo-MuLV infection. Our findings suggest that retroviruses in the same receptor class can exhibit different host ranges due to single amino acid differences in their cellular receptor.

3T3 Cells↗
PubMed1993

Characterization of cloned somatostatin receptors SSTR4 and SSTR5.

The recent molecular cloning of the genes and cDNAs encoding multiple somatostatin (SRIF) receptor subtypes has allowed for the individual expression of these receptors in mammalian cells and characterization of their respective pharmacological profiles. Previously, we fully described and compared the pharmacological properties of the first three SRIF receptor subtypes, SRIF receptor type (SSTR)1, SSTR2, and SSTR3. In the present study, we have investigated the properties of the newly cloned SRIF receptor subtypes SSTR4 and SSTR5 with regard to pharmacological profiles, the regulation of high affinity agonist binding to these receptors by stable GTP analogues, Na+, or prior exposure to agonists, and the inhibition of forskolin-stimulated cAMP accumulation mediated by these receptors. We labeled SSTR4 and SSTR5 expressed in Chinese hamster ovary (CHO-K1) and COS-1 cells, respectively, with the metabolically stable SRIF analogue 125I-CGP 23996. Radioligand binding competition studies were performed using SRIF analogues of differing structures, including hexapeptide analogues similar to MK-678, octapeptide analogues similar to SMS 201-995, pentapeptide analogues similar to c[Ahep-Phe-D-Trp-Lys-Thr(Bzl)], and linear SRIF analogues. SSTR4 bound compounds in all structural classes with high to moderate affinities, and several compounds were identified that are > 100-fold selective for SSTR4, compared with the other cloned SRIF receptors, including the linear SRIF analogue BIM-23052 and the CGP 23996-like SRIF analogue L-362,855. In contrast, SSTR5 bound very few SRIF analogues with high affinity. Both receptors could be regulated by prior exposure to agonist. In addition, agonist binding to SSTR4 was reduced by stable GTP analogues, Na+, and pertussis toxin, but agonist binding to SSTR5 was not affected by these treatments. SSTR4 is efficiently coupled to the inhibition of adenylyl cyclase activity, whereas SSTR5 appears not to couple to this cellular effector system. Such differences between the cloned SRIF receptors provide useful strategies for identifying regions of these receptor subtypes that may be involved in ligand-binding specificities and G protein and cellular effector system coupling. The identification of subtype-selective SRIF analogues may lead to more specific therapeutic interventions.

Amino Acid Sequence↗
PubMed1993

Characterization of the gamma-aminobutyric acidA receptor-channel complex composed of alpha 1 beta 2 and alpha 1 beta 3 subunits from rat brain.

The cloned alpha 1, beta 2 and beta 3 subunits of the gamma-aminobutyric acid (GABA)A receptor-channel complex from rat brain were coexpressed as alpha beta complexes in cultured Chinese hamster ovary cells. Electrophysiological characterization of alpha 1 beta 2 and alpha 1 beta 3 receptor subunit arrangements was performed utilizing patch electrodes in the whole-cell recording configuration. The reversal potential of the current activated by either GABA or muscimol corresponded to that expected for Cl- ions and was dependent on the Cl- gradient. The dose response to GABA for activation of Cl- currents by either subunit combination displayed similar potencies. Currents were partially blocked by the reversible antagonist bicuculline. (-)Pentobarbital was ineffective by itself, but potentiated responses to GABA. The steroid alphaxalone (3 alpha-hydroxy 5 alpha-pregnane 11,20-dione) produced just-detectable inward currents, but did not potentiate GABA-activated currents. Diazepam was completely ineffective. The kinetics and conductance of the Cl- ion channels were inferred from spectral analysis of agonist-induced current fluctuations. Both kinetics and conductance were dependent on agonist structure.

Animals↗
PubMed1992

Differential and transient expression of GABAA receptor alpha-subunit mRNAs in the developing rat CNS.

The expression of mRNAs coding for alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of the GABAA neurotransmitter receptor was followed during the development of the rat CNS by in situ hybridization histochemistry. Expression of these subunit mRNAs in tissue sections of embryonic day 15 and 17 (E15, E17) whole rat and in brain at ages greater than E17 to adult were varied, transient, and region specific. Subunit mRNAs first detected at E15 were those coding for the alpha 2 and alpha 3 subunits. At E17, alpha 2, alpha 3, and alpha 5 mRNAs were present in abundance in numerous areas in the CNS, with lower but significant amounts of alpha 6 being present in the cortical neuroepithelial layers. However, alpha 6 subunit mRNA expression in the cortex declined until little or no alpha 6 mRNA was detected at E19. alpha 1 subunit mRNA first appeared at E19 in the cortex, followed by expression in the hippocampus by postnatal 5 (PN5). Particularly high expression of alpha 2 and alpha 5 subunit mRNAs was detected throughout the developing CNS, but they were most abundant in the olfactory bulb neurons. The high levels of alpha 2 and alpha 5 subunit mRNAs began to decline around PN5 to the amounts observed in adult. These results demonstrate that numerous GABAA receptor alpha-subunits are expressed before birth in a region- and age-specific manner. This complex and varied expression supports the hypothesis that GABA may play a role in cellular and synaptic differentiation.

Animals↗
PubMed1992

Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28.

Using the polymerase chain reaction technique with degenerative primers, we obtained from a rat pituitary cDNA library a cDNA fragment, rAP236, that exhibited considerable homology to known receptors that belong to the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. Oligonucleotides to this fragment were used as probes to obtain a full-length cDNA from the rat pituitary cDNA library. This clone, rAP6-26, encoded a 383-amino acid protein with seven putative transmembrane domains that are characteristic of G protein-coupled receptors. The predicted amino acid sequence of the rAP6-26 cDNA exhibits 56-66% homology to recently cloned somatostatin (SRIF) receptors. Membranes prepared from COS-7 cells transfected with the rAP6-26 cDNA showed specific binding of 125I-Tyr11-SRIF, thus identifying the cDNA clone as a novel SRIF receptor. Radioligand binding competition analysis using somatostatin-28 (SRIF-28) and a number of cyclic SRIF analogs revealed that SRIF-28 was the most potent competitor of 125I-Tyr11-SRIF binding, with a approximately 30-fold greater affinity for the receptor than that of SRIF. In addition, binding of 125I-Tyr11-SRIF was markedly reduced in the presence of Na+ ions and GTP, indicating coupling of rAP6-26 receptors to inhibitory G proteins in COS-7 membranes. In adenylyl cyclase assays, forskolin-induced cAMP accumulation was inhibited by SRIF and SRIF-28, thus confirming that the rAP6-26 cDNA encodes a functional receptor protein. By Northern blot analysis, a approximately 2.6 kilobase mRNA encoding the receptor was present in the pituitary but not in the liver, small intestine, kidney, pancreas, cerebellum, or cortex. Lack of receptor mRNA expression in the brain was confirmed by in situ hybridization histochemical studies. Thus, we report the cloning of a novel rat pituitary SRIF receptor, termed SSTR4, that has marked preferential affinity for SRIF-28 and is linked to inhibition of adenylyl cyclase.

Amino Acid Sequence↗
PubMed1991

GABAA receptors containing alpha 1 and beta 2 subunits are mainly localized on neurons in the ventral pallidum.

The gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is important in the regulation of locomotion. Thus, stimulation and inhibition of GABAA receptors in the VP can alter locomotor activity. To determine whether the GABAA receptors are located presynaptically on accumbens efferents to the VP or postsynaptically on neurons intrinsic to the VP two experiments were performed. In the first, quinolinic acid lesions of the nucleus accumbens did not alter [3H]muscimol binding in the VP, while lesions in the VP significantly reduced (60-80%) binding as measured by light microscopic receptor autoradiography. In the second experiment, in situ hybridization with oligonucleotide probes for mRNAs of the alpha 1 and beta 2 subunits of the GABAA receptor was examined in the nucleus accumbens and VP. No mRNA for either subunit was observed in the nucleus accumbens, although many positively labeled neurons were present within the VP. By contrast, a moderate to high density of cells in both the nucleus accumbens and VP contained mRNA for glutamic acid decarboxylase. These data argue that the majority of GABAA receptors in the VP are not located presynaptically on axonal terminals originating from neurons in the nucleus accumbens.

Animals↗
PubMed1991

Oligonucleotides antisense to the interleukin 1 receptor mRNA block the effects of interleukin 1 in cultured murine and human fibroblasts and in mice.

Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics.

Animals↗
PubMed1991

Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells.

A rat D2L dopamine receptor, a splice variant of the D2 receptor, has recently been cloned. When transfected into and stably expressed in Chinese hamster ovary cells, these receptors mediate the inhibition of both basal and forskolin-stimulated cAMP production, as previously described. We examined what role this receptor might play in the production of the second messenger arachidonic acid. The calcium ionophore A23187 stimulated the release of arachidonic acid, and this release of arachidonic acid was potentiated by dopamine in a concentration-dependent manner. Dopamine alone, however, had no effect on arachidonic acid release. Quinpirole, a D2-selective agonist, augmented A23187-stimulated arachidonic acid release, and sulpiride, a D2-selective antagonist, blocked this augmentation. cAMP analogs and agents that activate adenylyl cyclase were utilized in an attempt to overcome this dopamine effect. Forskolin, prostaglandin E2, dibutyryl-cAMP, 8-(4-chlorophenylthio)-cAMP, and pertussis toxin all had no appreciable effect on either A23187-stimulated arachidonic acid release or the dopamine enhancement. Inhibition of protein kinase C using long term phorbol ester desensitization and pharmacological inhibitors diminished the dopamine potentiation of arachidonic acid release. These results suggest that the D2 receptor may be increasing the release of arachidonic acid by a mechanism involving protein kinase C but independent of the D2 receptor's inhibition of adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1991

Cloning and expression of an A1 adenosine receptor from rat brain.

We have used the polymerase chain reaction technique to selectively amplify guanine nucleotide-binding regulatory protein (G protein)-coupled receptor cDNA sequences from rat striatal mRNA, using sets of highly degenerate primers derived from transmembrane sequences of previously cloned G protein-coupled receptors. A novel cDNA fragment was identified, which exhibits considerable homology to various members of the G protein-coupled receptor family. This fragment was used to isolate a full-length cDNA from a rat striatal library. A 2.2-kilobase clone was obtained that encodes a protein of 326 amino acids with seven transmembrane domains, as predicted by hydropathy analysis. Stably transfected mouse A9-L cells and Chinese hamster ovary cells that expressed mRNA for this clone were screened with putative receptor ligands. Saturable and specific binding sites for the A1 adenosine antagonist [3H]-1,3-dipropyl-8-cyclopentylxanthine were identified on membranes from transfected cells. The rank order of potency and affinities of various adenosine agonist and antagonist ligands confirmed the identity of this cDNA clone as an A1 adenosine receptor. The high affinity binding of A1 adenosine agonists was shown to be sensitive to the nonhydrolyzable GTP analog guanylyl-5'-imidodiphosphate. In adenylyl cyclase assays, adenosine agonists inhibited forskolin-stimulated cAMP production by greater than 50%, in a pharmacologically specific fashion. Northern blot and in situ hybridization analyses of receptor mRNA in brain tissues revealed two transcripts of 5.6 and 3.1 kilobases, both of which were abundant in cortex, cerebellum, hippocampus, and thalamus, with lower levels in olfactory bulb, striatum, mesencephalon, and retina. These regional distribution data are in good agreement with previous receptor autoradiographic studies involving the A1 adenosine receptor. We conclude that we have cloned a cDNA encoding an A1 adenosine receptor linked to the inhibition of adenylyl cyclase activity.

Amino Acid Sequence↗
PubMed1990

D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons.

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗