Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1996-09-12
2000-04-04
Teng, Sally P.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
536 235, 4352523, 43525411, 4353201, 435325, C12N 1512, C07K 14705
Patent
active
060460261
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention pertains to DNA sequences that encode opiorph receptor polypeptide(s). Opiorph receptor polypeptides are highly related to known opioid receptors. The invention also encompasses the opiorph receptors and antibodies directed against these polypeptides.
BACKGROUND TO THE INVENTION
Opioid receptors are members of the receptor superfamily of polypeptides that typically have seven transmembrane domains and that are functionally coupled to G proteins. cDNAs encoding several types of opioid receptors have been cloned, including the mu, delta, and kappa opioid receptors (Wang et al., (1983), Proc. Natl. Acad. Sci., USA, 90:10230; Chen et al., (1993), Mol. Pharmacol., 44:8; Evans et al., (1992), Science, 258:1952; Kieffer et al., Proc. Natl. Acad. Sci., USA, 89:12048; Yasuda et al, (1993), Proc. Natl. Acad. Sci., USA, 90:6736.)
It is believed that the proteins encoded by these cDNAs mediate many of the physiological effects of endogenous opioid agonist peptides, such as, for example, met- and leu-enkephalin, beta-endorphin, and dynorphin, as well as opiate alkaloids such as morphine (Jaffe and Martin, in The Pharmacological Basis of Therapeutics, A. G. Gilman et al., eds., MacMillan. New York, 1985, pages 491-531). These physiological effects, which occur in both the central and peripheral nervous system, include analgesia, effects, which occur in both the central and peripheral nervous system, include analgesia, drowsiness, mood changes, respiratory depression, decreased gastrointestinal mobility, nausea, vomiting, and other alterations in the endocrine and autonomic nervous system.
Another family of opioid receptors, the epsilon receptors, have been studied in brain and immune tissue (Nock et al., (1993), J. Pharm. Expl. Therap., 264:349; Sibinga et al., (1988), Ann. Rev. Immunol., 6:219). Epsilon receptors, in the immune system, appear to mediate the effects of beta-endorphin on the cytotoxicity of monocytes, on conversion of precursor cells into killer cells, and on chemotaxis.
It has been found that some opioid effects may be mediated by receptors other than the known mu, delta, and kappa receptors. This indicates the existence of subtypes of each of these receptor classes. For example, two subtypes of mu-receptor, two subtypes of delta receptor, and three subtypes of kappa receptor have been identified pharmacologically (Pasternak, Clin.Neuropharm. 16:1, 1993).
New opioid receptor polypeptides have now been identified by isolating cDNAs that are homologous to known receptors.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A, 1B, 1C and 1D is an illustration of DNA sequences encoding rat opiorph receptor polypeptides SEQ ID NO:1.
FIG. 2 is an illustration of the predicted amino acid sequences of rat opiorph receptor polypeptides SEQ ID NO:2.
FIGS. 3A, 3B, and 3C illustrates a comparison among an opiorph receptor polypeptide sequence of FIG. 2 (OR7) (rXor1) and the amino acid sequences of rat delta opioid receptor polypeptide (rDor1SEQ ID NO:3), rat mu opioid receptor polypeptide (rMor1SEQ ID NO:4), and rat kappa opioid receptor polypeptide (rKor1SEQ ID NO:5). Putative transmembrane domains are shaded. The extra amino acids encoded by the large splice variant of the opiorph receptor polypeptides are shown as an insert between amino acids 193 and 194 of SEQ ID NO:2.
FIG. 4 is a dendrogram illustrating the evolutionary relatedness of the opiorph receptor polypeptides of FIG. 2 and other G-protein-linked receptor polypeptides.
FIG. 5 is an illustration of an autoradiogram showing the tissue distribution of mRNA encoding an opiorph receptor polypeptide, as determined by reverse transcription-polymerase chain reaction (RT-PCR) using, as a template, RNA derived from different rat tissues and cell lines. The RT-PCR products were resolved in an agarose gel. The left lane contains molecular mass markers, after which the lanes are numbered sequentially 1-16 from left to right.
FIG. 6A is an illustration of an autoradiogram showing the tissue distribution of mRNA encoding an opiorph
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Eppler Cecil Mark
Hulmes Jeffrey D.
Ozenberger Bradley A.
American Cyanamid Company
Teng Sally P.
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