Catherine Abbadie
Memorial Sloan Kettering Cancer Center
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Catherine Abbadie.
The Journal of Comparative Neurology | 2000
Catherine Abbadie; Ying-Xian Pan; Gavril W. Pasternak
The present study examined immunohistochemically the regional distribution of the mu opioid receptor splice variant MOR‐1C by using a rabbit antisera generated against the C‐terminal peptide sequences and compared it with MOR‐1. Overall, the distribution of MOR‐1C–like immunoreactivity (–LI) differed from MOR‐1–LI. Both MOR‐1C–LI and MOR‐1–LI were prominent in a few central nervous system regions, including the lateral parabrachial nucleus, the periaqueductal gray, and laminae I‐II of the spinal trigeminal nuclei and the spinal cord. In the striatum, hippocampal formation, presubiculum and parasubiculum, amygdaloid nuclei, thalamic nuclei, locus coeruleus, and nucleus ambiguous MOR‐1–LI predominated, whereas MOR‐1C–LI was absent or sparse. Conversely, MOR‐1C–LI exceeded MOR‐1–LI in the lateral septum, the deep laminae of the spinal cord, and most hypothalamic nuclei such as the median eminence, periventricular, suprachiasmatic, supraoptic, arcuate, paraventricular, ventromedial, and dorsomedial nuclei. Double‐labeling studies showed colocalization of the two receptors in neurons of the lateral septum, but not in the median eminence or in the arcuate nucleus, even though both MOR‐1 isoforms were expressed. Because both MOR‐1 and MOR‐1C are derived from the same gene, these differences in regional distribution represent region‐specific mRNA processing. The regional distributions reported in this study involve the epitope seen by the combinations of exons 7, 8, and 9. However, if other MOR‐1 variants containing exons 7, 8, and 9 exist, the antisera would not distinguish between them and MOR‐1C. J. Comp. Neurol. 419:244–256, 2000.
Neuroscience | 2000
Catherine Abbadie; Ying-Xian Pan; Carrie T. Drake; Gavril W. Pasternak
The present study examined immunohistochemically the CNS distributions of a splice variant of the mu-opioid receptor, MOR-1D, in both rats and mice. In MOR-1D, exon 4 of MOR-1 is replaced by two additional exons that code for seven amino acids. Using rabbit antisera, we compared immunohistochemically the regional distribution of a C-terminal epitope of MOR-1D to that of a C-terminal epitope from MOR-1 and a C-terminal epitope from another splice variant, MOR-1C. The general distribution of MOR-1D-like immunoreactivity was similar in both mouse and rat. MOR-1D-like immunoreactivity was seen in the dentate gyrus and in the mossy fibers of the hippocampal formation, the nucleus of the solitary tract and the area postrema, the inferior olivary nucleus, the nucleus ambiguous, the spinal trigeminal nucleus and the spinal cord. MOR-1D-like immunoreactivity was not observed in some regions containing dense MOR-1-like immunoreactivity, such as the striatum or the locus coeruleus. In regions containing MOR-1, MOR-1C and MOR-1D, the pattern of each variant was unique.MOR-1D and MOR-1C are splice variants of the cloned mu-opioid receptor MOR-1. Although they differ only at the tip of the carboxy terminus, they show marked differences in their regional distributions, as determined immunohistochemically by epitopes in their unique carboxy termini. Since the splice variants are derived from the same gene, these differences in regional distribution imply region-specific messenger RNA processing.
Neuroscience | 2001
Catherine Abbadie; Gavril W. Pasternak; Sue A. Aicher
Opioids inhibit nociceptive transmission at the level of the spinal cord, possibly through inhibition of neurotransmitter release by presynaptic mu opioid receptors (MORs) thus preventing the activation of ascending pathways and the perception of pain. Most nociceptive primary afferents are unmyelinated fibers containing peptides such as substance P and/or calcitonin gene-related peptide. However, few terminals contain both substance P and MOR. Recently, we identified new carboxy-terminal MOR splice variants that are localized in the superficial laminae of the dorsal horn. We now report the precise cellular distribution of two of these MOR-1 variants, MOR-1C (exon 7/8/9 epitope) and MOR-1D (exon 8/9 epitope), at the ultrastructural level. In the superficial laminae of the dorsal horn, the majority of the labeling of MOR-1C and MOR-1D was found in unmyelinated axons. This distribution contrasts with that of MOR-1 (exon 4 epitope), in which labeling is equally found in dendrites and soma, as well as in axons. The presence of dense core vesicles in many of the MOR-1C-like immunoreactive terminals implies that this splice variant might be involved in presynaptic inhibition of transmitter release from peptide-containing afferents to the dorsal horn. Consistent with this finding, confocal microscopy analyses showed that many MOR-1C profiles in laminae I-II also contained calcitonin gene-related peptide, whereas fewer MOR-1 profiles contained either substance P or calcitonin gene-related peptide in this same region. From these findings we suggest that there are differential distributions of MOR-1 splice variants as well as distinct peptide colocalizations in the dorsal horn.
Neuroreport | 2001
Catherine Abbadie; Gavril W. Pasternak
The mu opioid receptor MOR-1 is internalized by many mu agonists, but not morphine. To see whether differences in the intracellular carboxy terminus influences internalization, we examined internalization of a splice variant of the mu opioid receptor, MOR-1C, in the lateral septum of the mouse in vivo. Following intracerebroventricular (i.c.v.) saline treatment, MOR-1C-like immunoreactivity (LI) within neurons in naive mice was found predominantly in clusters close to the plasma membrane. Following either intracerebroventricular [d-Ala2, MePhe4,Gly(ol)5]enkephalin (DAMGO) or morphine, MOR-1C-LI clustered into endosomes in the cytoplasm. This effect was suppressed by prior administration of the opioid antagonist naloxone. In contrast, only DAMGO, and not morphine, internalized MOR-1-LI. These results illustrate differences in internalization between two MOR-1 variants that have alternative splicing at the COOH terminus.
Neuroreport | 2000
Catherine Abbadie; Gultekin Sh; Gavril W. Pasternak
The present study examined the distribution in the human spinal cord of a unique carboxy terminus sequence contained within MOR-IC, one of the recently described splice variants of the cloned mu opioid receptor gene MOR-I. Although MOR-I-like immunoreactivity (LI) and delta opioid receptor-like immunoreactivity were observed only in the superficial laminae, MOR-IC-LI was abundant in the superficial laminae of the dorsal horn and around the central canal. In the substantia gelatinosa, MOR-IC-LI was found in small diameter axonal elements, the cytoplasm and the plasmalemma of small spinal neurons and dendrites in inner lamina II and in some fibers within Lissauers tract. These studies imply the presence of MOR-IC in human spinal cord and its distribution suggests that it plays a role in the control of pain processing.
European Journal of Neuroscience | 2002
Catherine Abbadie; Grace C. Rossi; A. Orciuolo; James E. Zadina; Gavril W. Pasternak
The present study characterizes the relationship between the endogenous mu opioid peptides endomorphin‐1 (EM‐1) and endomorphin‐2 (EM‐2) and several splice variants of the cloned mu opioid receptor (MOR‐1) encoded by the mu opioid receptor gene (Oprm). Confocal laser microscopy revealed that fibers containing EM‐2‐like immunoreactivity (‐LI) were distributed in close apposition to fibers showing MOR‐1‐LI (exon 4‐LI) and to MOR‐1C‐LI (exons 7/8/9‐LI) in the superficial laminae of the lumbar spinal cord. We also observed colocalization of EM‐2‐LI and MOR‐1‐LI in a few fibers of lamina II, and colocalization of EM‐2‐LI and MOR‐1C‐LI in laminae I–II, and V–VI. To assess the functional relevance of the MOR‐1 variants in endomorphin analgesia, we examined the effects of antisense treatments that targeted individual exons within the Oprm1 gene on EM‐1 and EM‐2 analgesia in the tail flick test. This antisense mapping study implied mu opioid receptor mechanisms for the endomorphins are distinct from those of morphine or morphine‐6β‐glucuronide (M6G).
Neuroscience | 2004
Catherine Abbadie; Ying-Xian Pan; Gavril W. Pasternak
The cloned mu opioid receptor MOR-1 undergoes alternative splicing. Extensive 3-splicing downstream from exon 3 leads to a number of C-terminal splice variants that are differentially expressed within the CNS. Recently, 5-splicing has been observed with eight additional variants containing exon 11, a new exon located approximately 10 kb upstream from exon 1 that is under the control of a different promoter located even further upstream. Three of these variants generate the same protein as MOR-1 itself, but under the control of the new exon 11 promoter. Three variants in which exon 11 is translated have been identified within the brain, including MOR-1G, MOR-1M and MOR-1N. The present paper defines immunohistochemically the distribution of these variants using an exon 11-specific antiserum. The expression of exon 11-like immunoreactivity (-LI) was seen primarily in the olfactory tubercle, caudate-putamen, globus pallidus and substantia nigra. We did not observe exon 11-LI in a number of regions expressing MOR-1. Within the caudate-putamen, the general pattern of labeling was diffuse, in contrast to the pattern seen with an exon 4-generated antiserum that labels MOR-1 itself. However, we did observe in the caudate-putamen co-expression of exon 4- and exon 11-LI in cells that were apposed to dopaminergic terminals. These results provide new insights regarding the potential physiological significance of these exon 11-containing variants.
Handbook of Chemical Neuroanatomy | 2002
Catherine Abbadie; Gavril W. Pasternak
Publisher Summary This chapter presents the identification and classification of Opioids receptors. Opioids have long played a major role in pharmacology, representing one of the oldest classes of clinically important pharmaceuticals. Like many drugs, they act through receptors and the opioid receptors were among the first to be identified in binding assays. All the opioid receptors share the ability to mediate analgesia. Since most opiate and opioid peptides show only modest selectivity among the receptors, and all the receptors can elicit a similar pharmacological response, it has been difficult to dissect the actions of each alone. With the ability to label these receptors came the opportunity to identify precisely their localization within the central nervous system using autoradiographic approaches. These early studies defining their distributions used various opioid ligands and quickly established the presence of opioid binding sites in brain regions presumed to be important in mediating opioid actions. However, as understanding of opioid receptors has expanded, it has become apparent that opioids act through a family of receptors, as described in the chapter. Equally important, many of the ligands initially thought to be “selective” are now known not to be, complicating the interpretation of the earlier studies.
Molecular Pharmacology | 1999
Ying-Xian Pan; Jin Xu; Elizabeth Bolan; Catherine Abbadie; Albert Chang; Amy Zuckerman; Grace C. Rossi; Gavril W. Pasternak
Journal of Pharmacology and Experimental Therapeutics | 2002
Grace C. Rossi; Michael J. Pellegrino; Randi Shane; Catherine Abbadie; Jessica Dustman; Charles Jimenez; Richard J. Bodnar; Gavril W. Pasternak; Richard G. Allen