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At least 19 recordsLinked to original sources
PubMed1995

A human orphan calcitonin receptor-like structure.

A novel calcitonin receptor-like protein of 461 amino acids with seven putative transmembrane domains has been identified through molecular cloning in a cDNA library of the human cerebellum. 91% and 56% of the amino acids are identical in a rat orphan calcitonin receptor-like sequence and the human calcitonin receptor, respectively. 5.2 kb mRNA is predominantly expressed in the lung, heart and kidney. Specific binding of 125I-labeled salmon calcitonin and human calcitonin gene-related peptide-I to COS-7 cells transiently transfected with the receptor cDNA was less then 0.5%. Cellular cAMP accumulation was indistinguishable in cDNA transfected and non-transfected control COS-7 and renal tubular cells from the American opossum stimulated with human and salmon calcitonin, human calcitonin gene-related peptide-I and -II, human amylin, human adrenomedullin, lizard helodermin, salmon stanniocalcin and chicken parathyroid hormone-related protein. The receptor-like protein whose ligand remains to be discovered belongs to the family of receptors of calcitonin, parathyroid hormone, secretin, vasointestinal peptide and pituitary adenylate cyclase-activating polypeptide.

Amino Acid Sequence↗
PubMed1999

The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.

Adrenomedullin, a potently hypotensive peptide isolated from human pheochromocytoma, is known to elicit a rise in cAMP levels within mammalian endothelial and smooth muscle cells. Until now, however, little has been known about the adrenomedullin receptor. Recently, a group called receptor activity-modifying proteins that complex with the calcitonin receptor-like receptor, and thereby regulate its transport and ligand specificity, were identified. Here we show that mRNA for both the calcitonin receptor-like receptor and the receptor activity-modifying protein 2, but not the receptor activity-modifying protein 1 or receptor activity-modifying protein 3, are expressed in human endothelial and vascular smooth muscle cells. We also found that adrenomedullin increased cAMP levels in HeLa EBNA and 293 EBNA cells, expressing both the receptor activity-modifying protein 2 and calcitonin receptor-like receptor proteins. Thus, the receptor activity-modifying protein 2/calcitonin receptor-like receptor complex apparently serves as a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.

Adrenomedullin↗
PubMed1998

The CGRP receptor can couple via pertussis toxin sensitive and insensitive G proteins.

Swiss 3T3 cell lines were constructed co-expressing receptor activity modifying protein (RAMP) 1 with the calcitonin receptor-like receptor (CRLR), and showed 125I-calcitonin-gene-related peptide (CGRP) 1 binding indicative of a type I CGRP receptor. Application of CGRP1 led to an increase in cAMP, which in 2/5 cell lines was augmented following pertussis toxin (PTX) pre-treatment. In Xenopus oocytes, expression of RAMP1, which potentiates an endogenous CGRP receptor, led to constitutive activation of co-expressed GIRK potassium channels. This potassium current was increased following CGRP application or co-expression of CRLR, but decreased by PTX or co-expression of transducin. We conclude that the CGRP receptor can signal to both PTX sensitive and insensitive G proteins.

3T3 Cells↗
PubMed1999

The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor.

The calcitonin receptor-like receptor (CRLR) can function as either a receptor for calcitonin gene-related peptide (CGRP) or for adrenomedullin (ADM), depending upon the coexpression of a novel family of single transmembrane proteins, which we have called receptor activity modifying proteins or RAMPs. RAMPs 1, 2, and 3 transport CRLR to the plasma membrane with similar efficiencies, however RAMP1 presents CRLR as a terminally glycosylated, mature glycoprotein and a CGRP receptor, whereas RAMPs 2 and 3 present CRLR as an immature, core glycosylated ADM receptor. Characterization of the RAMP2/CRLR and RAMP3/CRLR receptors in HEK293T cells by radioligand binding (125I-ADM as radioligand), functional assay (cAMP measurement), or biochemical analysis (SDS-polyacrylamide gel electrophoresis) revealed them to be indistinguishable, even though RAMPs 2 and 3 share only 30% identity. Chimeric proteins were created with the transmembrane and cytosolic portions of RAMP1 associated with the amino terminus of RAMP2 (RAMP2/1) and vice versa (RAMP1/2). Coexpression of RAMP2/1 with CRLR formed a core glycosylated ADM receptor, whereas the RAMP1/2 chimera generated both core glycosylated and mature forms of CRLR and enabled both ADM and CGRP receptor binding. Hence, the glycosylation state of CRLR appears to correlate with its pharmacology.

Adrenomedullin↗
PubMed1998

Expression of calcitonin receptor-like receptor and receptor-activity-modifying proteins in human cranial arteries.

Recently a new type of proteins modulating the pharmacological profile of the calcitonin receptor-like receptor (CRLR) were identified. The receptor-activity-modifying proteins (RAMPs) were shown to be essential for the expression of a functional CRLR and furthermore the RAMPs seemed to modify ligand selectivity of CRLR: coexpression of CRLR and RAMP1 resulted in a CGRP1 type of receptor while an adrenomedullin receptor resulted when CRLR and RAMP2 were coexpressed. In the present study significant molecular expression of CRLR concomitant with RAMP1, 2 and 3 were demonstrated in human meningeal, cerebral and temporal arteries by use of reverse transcriptase polymerase chain reactions (RT-PCR). These findings support previous studies demonstrating functional CGRP1 receptors in human cranial arteries. Furthermore the present study suggests the potential for functional adrenomedullin receptors in human cranial arteries.

Calcitonin Receptor-Like Protein↗
PubMed1999

A receptor activity modifying protein (RAMP)2-dependent adrenomedullin receptor is a calcitonin gene-related peptide receptor when coexpressed with human RAMP1.

Adrenomedullin (ADM) and alpha- and beta-calcitonin (CT) gene-related peptide (alpha-, betaCGRP) are structurally related vasodilatory peptides with homology to CT and amylin. An originally orphan human CT receptor-like receptor (hCRLR) is a Gs protein-coupled CGRP or ADM receptor when coexpressed with recently identified human single transmembrane domain receptor activity modifying proteins 1 (hRAMP1) or -2 (hRAMP2), respectively. Here, the function of the rat CRLR homologue (rCRLR) has been investigated in rat osteoblast-like UMR-106 cells and in COS-7 cells, in the absence and presence of hRAMP1 and -2 and combinations thereof. Transient expression of rCRLR in UMR-106 cells revealed an ADM receptor, and [125I]rat (r) ADM binding was enhanced with hRAMP2 and inhibited by 50% when hRAMP1 was coexpressed. Detectable [125I]h alphaCGRP binding required the presence of hRAMP1, and the expression of CGRP binding sites was unaffected by coexpressed hRAMP2. Specificity of ADM binding sites in [125I]rADM binding inhibition experiments was reflected by an over 1000-fold higher potency of rADM [half-maximal effective concentration = 0.19 +/- 0.05 nM (mean +/- SEM, n = 4)], compared with r alphaCGRP and r betaGRP, to induce a cAMP-responsive luciferase reporting gene (CRE-luc). In rCRLR and hRAMP1 cotransfected cells, expressing predominantly CGRP binding sites, r betaCGRP, r alphaCGRP, and rADM induced CRE-luc with half-maximal effective concentration of 0.27 +/- 0.17 nM, 0.37 +/- 0.27 nM, and 1.4 +/- 0.9 nM, respectively. In COS-7 cells, the results were comparable, but rCRLR required coexpressed hRAMP2 for ADM receptor function. This is consistent with higher levels of endogenous RAMP2 encoding messenger RNA in UMR-106, compared with COS-7 cells. In conclusion, the recognition of RAMP1 and -2 as mediators of CRLR expression as a CGRP or ADM receptor has been extended, with evidence that endogenous RAMP2 is sufficient to reveal an ADM receptor in UMR-106 cells. Inhibition of RAMP2-evoked ADM receptor expression by RAMP1 and generation of a CGRP receptor is consistent with competitive interactions of the different RAMPs with rCRLR.

Animals↗
PubMed1998

RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.

Calcitonin-gene-related peptide (CGRP) and adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP receptor or an adrenomedullin receptor, depending on which members of a new family of single-transmembrane-domain proteins, which we have called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are required to transport CRLR to the plasma membrane. RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported receptors are core-glycosylated and are adrenomedullin receptors.

3T3 Cells↗
PubMed1999

Co-expression of prepro-adrenomedullin with a putative adrenomedullin receptor gene in vascular smooth muscle.

The prepro-adrenomedullin (prepro-AM) gene encodes several biologically active peptides, including the potent vasodilator AM. At least part of the vasodilator action of AM appears to be mediated via interactions with receptors on vascular smooth muscle cells (VSMC); however, the specific receptors involved are not known. The aim of the present study was to identify putative AM receptor genes that are co-expressed with AM in cultured rat aortic VSMC that may mediate the actions of AM. AM mRNA was shown to be expressed in rat aortic VSMC cultures. In acute (4 h) secretion studies, only 20% of the total immunoreactive AM was intracellular, with the majority (80%) found in the medium, indicating active release of AM peptide from VSMC. Using highly specific ribonuclease protection analysis, mRNAs encoding three putative AM receptors [L1, calcitonin-receptor-like receptor (CRLR) and RDC1] were shown to be present at high concentrations in RNA extracts from lung. In cultured VSMC, however, whereas RDC1 mRNA was expressed at relatively high concentrations, transcripts encoding CRLR and L1 were not detected. The co-expression of prepro-AM mRNA with the RDC1 receptor implies that AM may act in a localized manner via this receptor to modulate VSMC function.

Adrenomedullin↗
PubMed1999

Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product.

Receptor activity-modifying proteins (RAMPs) are single-transmembrane proteins that transport the calcitonin receptor-like receptor (CRLR) to the cell surface. RAMP 1-transported CRLR is a calcitonin gene-related peptide (CGRP) receptor. RAMP 2- or RAMP 3-transported CRLR is an adrenomedullin receptor. The role of RAMPs beyond their interaction with CRLR, a class II G protein-coupled receptor, is unclear. In this study, we have examined the role of RAMPs in generating amylin receptor phenotypes from the calcitonin (CT) receptor gene product. Cotransfection of RAMP 1 or RAMP 3 with the human CT receptor lacking the 16-amino acid insert in intracellular domain 1 (hCTRI1-) into COS-7 cells induced specific 125I-labeled rat amylin binding. RAMP 2 or vector cotransfection did not cause significant increases in specific amylin binding. Competition-binding characterization of the RAMP-induced amylin receptors revealed two distinct phenotypes. The RAMP 1-derived amylin receptor demonstrated the highest affinity for salmon CT (IC50, 3.01 +/- 1.44 x 10(-10) M), a high to moderate affinity for rat amylin (IC50, 7.86 +/- 4.49 x 10(-9) M) and human CGRPalpha (IC50, 2.09 +/- 1.63 x 10(-8) M), and a low affinity for human CT (IC50, 4.47 +/- 0.78 x 10(-7) M). In contrast, whereas affinities for amylin and the CTs were similar for the RAMP 3-derived receptor, the efficacy of human CGRPalpha was markedly reduced (IC50, 1.12 +/- 0.45 x 10(-7) M; P <.05 versus RAMP 1). Functional cyclic AMP responses in COS-7 cells cotransfected with individual RAMPs and hCTRI1- were reflective of the phenotypes seen in competition for amylin binding. Confocal microscopic localization of c-myc-tagged RAMP 1 indicated that, when transfected alone, RAMP 1 almost exclusively was located intracellularly. Cotransfection with calcitonin receptor (CTR)I1- induced cell surface expression of RAMP 1. The results of experiments cross-linking 125I-labeled amylin to RAMP 1/hCTR-transfected cells with bis succidimidyl suberate were suggestive of a cell-surface association of RAMP 1 and the receptors. Our data suggest that in the CT family of receptors, and potentially in other class II G protein-coupled receptors, the cellular phenotype is likely to be dynamic in regard to the level and combination of both the receptor and the RAMP proteins.

Animals↗
PubMed1994

Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in feline ventral roots and pia mater.

The spinal pia mater receives a rich innervation of small sensory axons via the ventral roots. Other sensory axons enter the ventral roots but end blindly or turn abruptly in hairpin loop-like formations and continue in a distal direction. In the present study, the content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated with these different types of sensory axons was assessed with light and electron microscopic immunohistochemical techniques. In addition, the binding of antibodies against synthetic peptides representing unique sequences of residues in the products of the trk and trkB protooncogenes was analyzed. These genes encode membrane spanning proteins, which have been shown to constitute specific high affinity binding sites for several members of the nerve growth factor family of neurotrophic factors. The results of the present study imply that the ventral root afferents comprise several different types of sensory axons, which all contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at least some of the presumed sensory fiber bundles in ventral roots and the pia mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal cells and nonneuronal cells of the ventral roots were shown to bind antibodies to both the trk and trkB gene products. The ventral root afferents seem to share their immunohistochemical pattern with pain-transducing axons at some other locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory axons that reach the central nervous system (CNS) through the ventral root indicate that ventral root afferents may be involved in sensory mechanisms, such as the ventral root pain reaction, as well as in the control of the pial blood vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities associated with unmyelinated fibers in ventral roots and the pia mater is discussed in relation to previous reports on postnatal plasticity in these axonal populations.

Animals↗
PubMed1993

Cat dental pulp after denervation and subsequent re-innervation: changes in blood-flow regulation and distribution of neuropeptide-, GAP-43- and low-affinity neurotrophin receptor-like immunoreactivity.

The effects of unilateral extramandibular inferior alveolar nerve injury on pulpal blood-flow responses to electrical stimulation and i.v. injections of substance P (SP) in cat mandibular canine teeth with a dentinal lesion were investigated with laser Doppler flowmetry. After blood-flow recordings, the teeth were fixed and the pulps were examined with light and electron microscopy. The distribution of pulpal SP, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), growth-associated protein (GAP-43) and low-affinity neurotrophin receptor (LANR)-like immunoreactivity was examined with immunohistochemical fluorescence microscopy. Blood-flow recordings, performed at 10 days and 1 month postoperatively, showed that vasodilation, occurring in control teeth after bipolar electrical stimulation of the tooth crown, was absent in the denervated pulps, whereas at 3 months, five of six teeth had regained responsiveness, although at a low level. There was enhanced vasodilation (by 370%) to SP injections (400 fmol i.v.) at 10 days in denervated pulps. Such supersensitivity was reduced at 1 month despite the apparent lack of nerve fibers, and the response fell further towards the level in control teeth at 3 months when pulpal axons reappeared. At 10 days and 1 month postoperatively, light and electron microscopy demonstrated that surgery had resulted in total pulpal denervation. At 3 and 6 months, a large number of regenerated pulpal axons reappeared, in accordance with previous findings. At 10 days and 1 month after nerve transection immunohistochemistry showed a complete loss of pulpal immunoreactivity to all the neuropeptides that were studied. At 3 and 6 months, neuropeptide immunoreactivity reappeared but far fewer number of pulpal nerve fibers were SP-, NKA- and CGRP-immunoreactive than under normal conditions, as demonstrated by double-labeling experiments with GAP-43- or LANR-antiserum. The results indicate that pulpal hemoregulatory functions, which are lost after denervation, do not return to normal levels after nerve regeneration. This malfunction may be caused by inadequate target re-innervation and/or a deficiency of neuropeptides in the re-innervated pulp.

Animals↗
PubMed1986

Binding sites of calcitonin gene-related peptide (CGRP): abundant occurrence in visceral organs.

Calcitonin gene-related peptide (CGRP) is a novel peptide amide of 37 amino acid residues, which was first identified as the product of alternative processing of RNA transcripts of the calcitonin gene in humans and rats. Using 125I-human CGRP (hCGRP) as the binding ligand and hCGRP or salmon calcitonin (sCT) as the specific inhibitor of binding, it was examined how the receptor-like binding sites distribute among rat tissues including the nervous system, which is already known to contain binding sites in discrete regions. Some visceral organs (liver, spleen and lung) and possibly the bone marrow of Wistar male rats (8-10 weeks old) were found to be relatively rich in these binding sites. The following parameters were calculated by Scatchard analysis of binding data for the cerebellum, spleen and liver; KD (nM) and Bmax (fmol/mg protein) were 0.61 and 408, 1.08 and 858, and 0.89 and 356, respectively. In these three tissues, both hCGRP and sCT were able to completely suppress the specific binding; the IC50s (nM) of hCGRP for the cerebellum, spleen and liver were 2.57, 2.29 and 3.02, respectively, and the IC50s (microM) of sCT 2.69, 0.41 and 1.78, respectively. The results obtained herein strongly suggest the physiological function of CGRP in these visceral organs including bone marrow.

Animals↗
PubMed2000

Multiple ramp domains are required for generation of amylin receptor phenotype from the calcitonin receptor gene product.

Calcitonin (CT), calcitonin gene-related peptide (CGRP), amylin, and adrenomedullin constitute a family of structurally related peptides that signal via either the calcitonin receptor-like receptor or the CT receptor, with receptor phenotype determined by coexpression of one of the three receptor activity-modifying proteins (RAMPs). The nature of the interaction between the receptor and RAMP was investigated using chimeras between RAMP1 and RAMP2 where the amino-terminal domain of RAMP1 was attached to the transmembrane domain and carboxy terminus of RAMP2 and called RAMP1/2, and vice versa for RAMP2/1. Cotransfection of wild-type or chimeric RAMPs with the insert-negative isoform of the human CT receptor (hCTR(I1-)) into COS-7 cells resulted in the expression of (125)I-rat amylin binding sites. Highest specific binding was observed when either RAMP1 or RAMP2/1 were cotransfected, indicating the importance of the RAMP transmembrane domain and/or carboxy terminus for the degree to which amylin receptors are expressed. In contrast, the phenotype generated was primarily determined by the amino terminus, with similar RAMP1- and RAMP1/2-induced receptor phenotypes that had higher affinity for human CGRPalpha and lower affinity for human calcitonin than the RAMP2- and RAMP2/1-induced receptors.

Amyloid↗
PubMed1985

Demonstration and characterization of a 1 alpha,25-(OH)2D3 receptor-like macromolecule in cultured rat pituitary cells.

Recent studies have demonstrated the importance of prolactin (PRL) and growth hormone (GH) in the regulation of 25-hydroxycholecalciferol-1 alpha-hydroxylase activity. We have previously shown that 1 alpha,25-dihydroxycholecalciferol (1 alpha,25-(OH)2D3) reduces PRL and GH production by a clonal strain of rat pituitary tumour cells (GH3). The biologically active form of vitamin D3, 1 alpha,25-(OH)2D3, acts via an initial binding to cytoplasmic receptor proteins in target cells, and we demonstrate in this study the presence of specific receptors for 1 alpha,25-(OH)2D3 in the GH3 cells. GH3 cell cytosol was incubated with [3H]1 alpha,25-(OH)2D3 at 0-4 degrees C. Maximal binding was obtained between 2 and 6 h, and Scatchard analysis showed one single class of binding sites with Kd of 0.33 +/- 0.05 nM (mean + SD) and a Bmax of 103 +/- 26 fmol/mg cytosol protein. Competitive binding experiments revealed the following potency order: 1 alpha,25-(OH)2D3 greater than 25-OHD3 greater than 1 alpha-OHD3, 24,25-(OH)2D3. In contrast, corticosterone, testosterone, progesterone and oestradiol showed negligible ability to displace [3H]1 alpha,25-(OH)2D3 from its receptor. Sucrose gradient ultracentrifugation in high salt concentration revealed that GH3 cell cytosol possessed at 3.7S [3H]1 alpha,25-(OH)2D3 receptor protein which was inactivated by heating and protease treatment, but not after incubation with DNase or RNase. The receptor protein aggregated in salt-free sucrose gradients since the 3.7S complex was shifted reversibly to a approximately 6S form. Isoelectric focussing localized most of the [3H]1 alpha,25-(OH)2D3 to a protein peak with an isoelectric point of approximately 6 (pI 5.8-6.2). Since this 1 alpha,25-(OH)2D3 receptor protein has similar properties as the corresponding 1 alpha,25-(OH)2D3 receptors found in normal rat tissues, we suggest that lactotropes and somatotropes represent true target cells for 1 alpha,25-(OH)2D3.

Animals↗
PubMed1998

Distribution of novel CGRP1 receptor and adrenomedullin receptor mRNAs in the rat central nervous system.

Recent cloning studies have isolated receptors which confer specific responsiveness to calcitonin gene related peptide (CGRP) and the related peptide adrenomedullin. Using in situ hybridisation, we demonstrate the heterogenous distribution of the mRNAs of two proposed CGRP1 receptors (RDC-1 and calcitonin receptor-like receptor, CRLR) in the rat brain. Adrenomedullin receptor mRNA was weakly expressed, principally in the cerebellum. These findings may assist in the determination of the function of these largely uncharacterised receptors.

Amygdala↗
PubMed1999

Characterization of a putative calcitonin receptor in IMR 32 human neuroblastoma cells.

In this study we characterized calcitonin (CT) receptors in human neuroblastoma IMR 32 cells. Saturation binding assays indicated that [125I]-human CT bound with high affinity to IMR 32 cell membranes (K(d) = 253.6 pM; Bmax = 3.84 fmol/ mg protein). In competition binding studies, human adrenomedullin displayed high affinity for these sites (IC50 = 30 nM) whereas human alpha calcitonin-gene related peptide (alphaCGRP; IC50 = 145 nM) and human amylin (IC50 = 415 nM) showed lower affinity. These peptides increased cAMP levels in viable cells; the relative potencies were: human CT > human adrenomedullin > human cCGRP > or = human amylin. The expression of mRNA coding for the published sequences of the human calcitonin receptor and of the human calcitonin receptor-like receptorwas evaluated by reverse transcriptase-polymerase chain reaction. Electrophoretic analysis did not confirm the occurrence of mRNA coding for the above mentioned receptors in these cells. This study suggests the presence of a novel, putative CT receptor in IMR 32 cells.

Adrenomedullin↗
PubMed1998

Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles.

Using immunohistochemistry and immunoelectron microscopy, the localization and regulation of delta-opioid receptor-like immunoreactivity were studied in dorsal root ganglia and spinal cord of normal rat and monkey, and after peripheral axotomy. Delta-opioid receptor-like immunoreactivity was observed in many small dorsal root ganglion neurons, and in the rat most of them contained substance P and calcitonin gene-related peptide. At the ultrastructural level, delta-opioid receptor-like immunoreactivity was localized in the Golgi complex, on the membrane of the large dense-core vesicles and on the membrane of and/or inside a type of large vesicle with an interior of low electron density. The latter vesicles were often in contact with multivesicular bodies. In the superficial dorsal horn of the spinal cord, most delta-opioid receptor-positive nerve fibers contain substance P and/or calcitonin gene-related peptide, both in rat and monkey. Also, in these nerve endings delta-opioid receptor-like immunoreactivity was found on the membrane of large dense-core vesicles and on the membrane of, or in, the lucent vesicles. Occasionally, delta-opioid receptor-like immunoreactivity was observed on the plasmalemma of the terminals, particularly when the vesicles were in exocytotic contact with the plasmalemma. Peripheral axotomy induced a decrease in delta-opioid receptor-like immunoreactivity both in cell bodies in the dorsal root ganglia and in terminals in the dorsal horn. These data suggest that the delta-opioid receptor may be a constituent of the membrane of large dense-core vesicles storing and releasing neuropeptides. It is suggested that upon exocytotic release of substance P and calcitonin gene-related peptide from large dense-core vesicles, there is a transient modification of the surface of the primary afferent terminals which leads to exposure of the receptor protein so that enkephalin released from adjacent terminals can activate the receptor. The decrease in delta-opioid receptors after axotomy indicates that delta-opioid receptor-mediated inhibitory effects are attenuated at the spinal level both in the rat and monkey.

Animals↗