Showing papers on "Receptor published in 1992"
TL;DR: Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% ientical in sequence, and these are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor sub Units.
Abstract: The N-methyl d-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% ientical in sequence These are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1) Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate-and NMDA-activated currents only when they were in heteromeric configurations with NR1 NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution
2,578 citations
TL;DR: Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor.
Abstract: Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction.
2,246 citations
TL;DR: Apolipoprotein E-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis, with severe yet viable phenotype that should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.
Abstract: Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process
2,202 citations
TL;DR: The simple methodology greatly enhances the production and rapid evaluation of random libraries of millions of peptides so that acceptor-binding ligands of high affinity can be rapidly identified and sequenced, on the basis of a "one-bead, one-peptide9 approach.
Abstract: OUR aim was to improve techniques for drug development by facilitating the identification of small molecules that bind with high affinity to acceptor molecules (for example, cell-surface receptors, enzymes, antibodies) and so to mimic or block their interaction with the natural ligand1,2. Previously such small molecules have been characterized individually on a serial basis. The systematic synthesis and screening of peptide libraries of defined structure represents a new approach. For relatively small libraries, predetermined sequence variations on solid-phase supports have been used3,4, and large libraries have been produced using a bacteriophage vector into which random oligodeoxynucleotide sequences have been introduced5–8, but these techniques have severe limitations. Here we investigate an alternative approach to synthesis and screening of peptide libraries. Our simple methodology greatly enhances the production and rapid evaluation of random libraries of millions of peptides so that acceptor-binding ligands of high affinity can be rapidly identified and sequenced, on the basis of a "one-bead, one-peptide9 approach.
2,037 citations
TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
2,032 citations
TL;DR: The murine and human MSH receptors (MSH-Rs) and a human ACTH receptor (ACTH-R) were cloned and define a subfamily of receptors coupled to guanine nucleotide-binding proteins that may include the cannabinoid receptor.
Abstract: Melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) regulate pigmentation and adrenal cortical function, respectively. These peptides also have a variety of biological activities in other areas, including the brain, the pituitary, and the immune system. A complete understanding of the biological activities of these hormones requires the isolation and characterization of their corresponding receptors. The murine and human MSH receptors (MSH-Rs) and a human ACTH receptor (ACTH-R) were cloned. These receptors define a subfamily of receptors coupled to guanine nucleotide-binding proteins that may include the cannabinoid receptor.
1,625 citations
1,482 citations
TL;DR: Three novel members of the Xenopus nuclear hormone receptor superfamily have been cloned and their multiplicity suggests the existence of hitherto unknown cellular signaling pathways for xenobiotics and putative endogenous ligands.
1,358 citations
TL;DR: A complementary DNA clone encoding a functional delta opioid receptor has been identified and shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8.
Abstract: Opiate drugs have potent analgesic and addictive properties. These drugs interact with receptors that also mediate the response to endogenous opioid peptide ligands. However, the receptors for opioids have eluded definitive molecular characterization. By transient expression in COS cells and screening with an iodinated analog of the opioid peptide enkephalin, a complementary DNA clone encoding a functional delta opioid receptor has been identified. The sequence shows homology to G protein-coupled receptors, in particular the receptors for somatostatin, angiotensin, and interleukin-8.
1,249 citations
TL;DR: CTLA4lg therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells and induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.
Abstract: Antigen-specific T cell activation depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (lg) G1 Fc region (CTLA4lg) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4lg therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells. In addition, CTLA4lg induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.
1,235 citations
TL;DR: The cloning of a ligand for CD40 that is expressed on the cell surface of activated T cells and mediates B-cell proliferation in the absence of co-stimulus, as well as IgE production in the presence of interIeukin-4 is reported.
Abstract: THE CD40 surface molecule is a 277-amino-acid glycoprotein expressed on B lymphocytes, epithelial cells and some carcinoma cell lines. Monoclonal antibodies against CD40 mediate a variety of effects on B lymphocytes, including induction of intercellular adhesion1,2, short- and long-term proliferation3–5, differentiation6,7 and enhanced tyrosine phosphorylation of proteins8. In addition, germinal centre centrocytes are prevented from undergoing apop-tosis by activation through CD40 and receptor for antigen9. These data indicate that CD40 could be a receptor for an unknown ligand with important functions in B-cell development and activation. This hypothesis is strengthened by the homology of the extracellular region of the CD40 molecule10with a family of cell-surface glycoproteins11,12that includes the receptors for nerve growth factor13,14 and tumour necrosis factor11,15,16. Here we report the cloning of a ligand for CD40 that is expressed on the cell surface of activated T cells and mediates B-cell proliferation in the absence of co-stimulus, as well as IgE production in the presence of interIeukin-4.
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TL;DR: A model of TNF receptor triggering that reconciles the seemingly conflicting data is proposed and it is proposed that the relative roles played by the two receptor types in signaling the diverse functions of T NF are less clear.
TL;DR: The molecular characteristics of the recently cloned dopamine receptors are reviewed and prospects for the cloning and identification of additional subtypes in this receptor family are discussed.
Patent•
10 Apr 1992TL;DR: In this article, a filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, is presented.
Abstract: Filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.
TL;DR: Using expression cloning, a cDNA clone is isolated encoding rat bone PTH/PTHrP receptor from rat osteosarcoma cells that is 78% identical to the opossum kidney receptor and indicates striking conservation of this receptor across distant mammalian species.
Abstract: Parathyroid hormone (PTH), a major regulator of mineral ion metabolism, and PTH-related peptide (PTHrP), which causes hypercalcemia in some cancer patients, stimulate multiple signals (cAMP, inositol phosphates, and calcium) probably by activating common receptors in bone and kidney Using expression cloning, we have isolated a cDNA clone encoding rat bone PTH/PTHrP receptor from rat osteosarcoma (ROS 17/28) cells The rat bone PTH/PTHrP receptor is 78% identical to the opossum kidney receptor; this identity indicates striking conservation of this receptor across distant mammalian species Additionally, the rat bone PTH/PTHrP receptor has significant homology to the secretin and calcitonin receptors but not to any other G protein-linked receptor When expressed in COS cells, a single cDNA clone, expressing either rat bone or opossum kidney PTH/PTHrP receptor, mediates PTH and PTHrP stimulation of both adenylate cyclase and phospholipase C These properties could explain the diversity of PTH action without the need to postulate other receptor subtypes
TL;DR: A random primed expression cDNA library was constructed from the RNA of NG 108-15 cells that encodes a 371-amino acid-residue protein presenting all the structural characteristics of receptors that interact with guanine nucleotide-binding proteins.
Abstract: A random primed expression cDNA library was constructed from the RNA of NG 108-15 cells Pools of plasmid DNA were transfected into COS cells, which were screened for their ability to bind 3H-labeled Tyr-D-Thr-Gly-Phe-Leu-Thr, a tritiated agonist for the delta-opioid receptor A cDNA was isolated that encodes a 371-amino acid-residue protein presenting all the structural characteristics of receptors that interact with guanine nucleotide-binding proteins Noticeable features are (i) the high hydrophobicity of the encoded protein, (ii) its low sequence similarity to both catecholamine receptors and peptide-binding receptors, although it presents the typical aspartate residue involved in catecholamine binding of the first group and the characteristic short third cytoplasmic loop of the second group When expressed in COS cells, the receptor exhibits pharmacological properties similar to those of the native receptor: high-affinity binding sites for 3H-labeled Tyr-D-Thr-Gly-Phe-Leu-Thr (Kd = 14 nM), stereospecific binding sites for the - enantiomers of levorphanol and naloxone, and the selectivity profile of a delta receptor, as determined by competition experiments with a set of mu-, delta-, and kappa-opioid ligands
TL;DR: This is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population and such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.
Abstract: THE dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors1–5. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia6,7, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors1. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4 receptor. A 48-base-pair sequence in the putative third cytoplasmic loop of this receptor exists either as a direct-repeat sequence (D4.2), as a fourfold repeat (D4.4) or as a sevenfold repeat (D4.7). Two more variant alleles were detected in humans. Expression of the complementary DNA for the three cloned receptor variants showed different properties for the long form (D4.7) and the shorter forms (D4.2, D4.4) with respect to clozapine and spiperone binding. To our knowledge, this is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population. Such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.
TL;DR: Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation and protein kinases mediate neurotransmitter receptor-controlled APP processing.
Abstract: Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing.
Journal Article•
TL;DR: The data indicate that alpha 4 and beta 2 subunits are associated with each other in at least one neuronal nicotinic receptor subtype that has high affinity for agonists and is significantly increased in the cortex of rats chronically treated with nicotine.
Abstract: The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated against nonhomologous domains of the various subunits comprising this receptor class. In all brain regions tested, only antisera generated against the alpha 4 and beta 2 subunits were able to immunoprecipitate specifically receptors labeled by [3H]cytisine. Thus, these sera were further characterized in order to validate and optimize their use in the immunoprecipitation protocol. Preincubation of solubilized receptors from rat forebrain with antisera generated against the alpha 2, alpha 3, alpha 5, beta 3, or beta 4 subunits did not decrease the amount of precipitable alpha 4 or beta 2 subunit. On the other hand, when either anti-alpha 4 or anti-beta 2 serum was used to immunoprecipitate solubilized receptors from rat forebrain, the supernatants contained little if any remaining receptors that could be specifically precipitated by either antibody. Because these antisera do not cross-react, the data indicate that alpha 4 and beta 2 subunits are associated with each other in at least one neuronal nicotinic receptor subtype that has high affinity for agonists. Moreover, these results imply that all alpha 4 subunits that are labeled by [3H]cystisine are coupled to beta 2 subunits. We also present evidence that the alpha 4/beta 2 subtype characterized in this report is significantly increased in the cortex of rats chronically treated with nicotine.
TL;DR: It is demonstrated here that the major TGF-beta 1-binding protein co-existing with T GF-beta receptors I and II on human umbilical vein endothelial cells is endoglin, as determined by specific immunoprecipitation of endoglins affinity-labeled with 125I-TGF- beta.
TL;DR: It is reported here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sST NF-Rs of spontaneous TNF activity decay.
Abstract: The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF-Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects.
TL;DR: A third subunit, the gamma chain, of the human interleukin-2 receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine receptor family was isolated.
Abstract: A third subunit, the gamma chain, of the human interleukin-2 receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine receptor family was isolated. The gamma chain is necessary for the formation of the high- and intermediate-affinity receptors, which consists of alpha beta gamma heterotrimers and beta gamma heterodimers, respectively. The IL-2R on murine fibroblastoid cells can be internalized after binding IL-2 only if the gamma chain is present; alpha and beta are insufficient for internalization. Thus, the gamma chain is an indispensable component of the functional IL-2R.
TL;DR: A cDNA encoding the murine Ah receptor (Ahb-1 allele for aromatic hydrocarbon responsiveness) has been isolated and characterized in this article, which revealed a region with similarity to the basic region/helix-loop-helix (BR/HLH) motif found in many transcription factors that undergo dimerization for function.
Abstract: A cDNA encoding the murine Ah receptor (Ahb-1 allele for aromatic hydrocarbon responsiveness) has been isolated and characterized. Analysis of the deduced protein sequence revealed a region with similarity to the basic region/helix-loop-helix (BR/HLH) motif found in many transcription factors that undergo dimerization for function. In addition to the BR/HLH domain, the N-terminal domain of the Ah receptor has extensive sequence similarity to the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein and two regulatory proteins of Drosophila, Sim and Per. Photoaffinity labeling and peptide mapping studies indicate that the Ah receptor binds agonist at a domain that lies within this conserved N-terminal domain. The Ah receptor appears to be a ligand-activated transcription factor with a helix-loop-helix motif similar to those found in a variety of DNA-binding proteins, including Myc and MyoD.
TL;DR: The cloning, functional expression, and tissue distribution of two different somatostatin receptors (SSTRs) are reported, showing that SSTR1 and SSTR2 are expressed at highest levels in jejunum and stomach and in cerebrum and kidney, respectively.
Abstract: Somatostatin is a tetradecapeptide that is widely distributed in the body. It acts on multiple organs including brain, pituitary, gut, exocrine and endocrine pancreas, adrenals, thyroid, and kidneys to inhibit release of many hormones and other secretory proteins. In addition, it functions as a neuropeptide affecting the electrical activity of neurons. Somatostatin exerts its biological effects by binding to specific high-affinity receptors, which appear in many cases to be coupled to GTP-binding proteins. Here we report the cloning, functional expression, and tissue distribution of two different somatostatin receptors (SSTRs). SSTR1 and SSTR2 contain 391 and 369 amino acids, respectively, and are members of the superfamily of receptors having seven transmembrane segments. There is 46% identity and 70% similarity between the amino acid sequences of SSTR1 and SSTR2. Stably transfected Chinese hamster ovary cells expressing SSTR1 or SSTR2 exhibit specific somatostatin binding, with an apparently higher affinity for somatostatin-14 than somatostatin-28, and NH2-terminally extended form of somatostatin-14. RNA blotting studies show that SSTR1 and SSTR2 are expressed at highest levels in jejunum and stomach and in cerebrum and kidney, respectively. A SSTR1 probe hybridized to multiple DNA fragments in EcoRI digests of human and mouse DNA, indicating that SSTR1 and SSTR2 are members of a larger family of somatostatin receptors. Thus, the biological effects of somatostatin are mediated by a family of receptors that are expressed in a tissue-specific manner.
TL;DR: Two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene, as revealed by cDNA cloning and structural analysis of the KGFR.
Abstract: Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene.
TL;DR: The receptor selectivity of the natriuretic peptide family was investigated using the homologous assay system with endogenous ligands and receptors of the same species and the rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats.
Abstract: To elucidate the ligand-receptor relationship of the natriuretic peptide system, which comprises at least three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and three receptors, the ANP-A receptor or guanylate cyclase-A (GC-A), the ANP-B receptor or guanylate cyclase-B (GC-B), and the clearance receptor (C-receptor), we characterized the receptor preparations from human, bovine, and rat tissues and cultured cells with the aid of the binding assay, Northern blot technique, and the cGMP production method. Using these receptor preparations, we examined the binding affinities of ANP, BNP, and CNP for the C-receptor and their potencies for cGMP production via the ANP-A receptor (GC-A) and the ANP-B receptor (GC-B). These analyses revealed the presence of a marked species difference in the receptor selectivity of the natriuretic peptide family, especially among BNPs. Therefore, we investigated the receptor selectivity of the natriuretic peptide family using the homologous assay system with endogenous ligands and receptors of the same species. The rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats. The rank order of potency for cGMP production via the ANP-A receptor (GC-A) was ANP greater than or equal to BNP much greater than CNP, but that via the ANP-B receptor (GC-B) was CNP greater than ANP greater than or equal to BNP. These findings on the receptor selectivity of the natriuretic peptide family provide a new insight into the understanding of the physiological and clinical implications of the natriuretic peptide system.
TL;DR: It is revealed that VIP receptor mRNA is widely distributed in neuronal cells of the adult rat brain, with a relatively high expression in the cerebral cortex and hippocampus, suggesting that they constitute a new subfamily of the Gs protein-coupled receptors.
Journal Article•
TL;DR: The distribution and abundance of 5-HT1A receptor mRNA in different rat brain areas generally correlate with those of the binding sites, suggesting that 5- HT1A receptors are predominantly somatodendritic receptors.
Abstract: In order to localize the cells expressing 5-HT1A receptors in the rat brain, we used in situ hybridization histochemistry to visualize the distribution of the mRNA coding for 5-HT1A receptors. Oligonucleotides derived from different parts of the coding region of the rat 5-HT1A receptor gene were used as hybridization probes. 5-HT1A binding sites were visualized on consecutive sections by receptor autoradiography using 3H-8-hydroxy-2-(di-n-propylamino)tetralin as ligand. The highest levels of hybridization were observed in the dorsal raphe nucleus, septum, hippocampus, entorhinal cortex, and interpeduncular nucleus. Positive hybridization signals were also present in other areas, such as the olfactory bulb; cerebral cortex; some thalamic and hypothalamic nuclei; several nuclei of the brainstem, including all the remaining raphe nuclei, nucleus of the solitary tract, and nucleus of the spinal tract of the trigeminus; and the dorsal horn of the spinal cord. The distribution and abundance of 5-HT1A receptor mRNA in different rat brain areas generally correlate with those of the binding sites, suggesting that 5-HT1A receptors are predominantly somatodendritic receptors.