Human somatostatin-like receptor

Details Human somatostatin-like receptor Human somatostatin-like receptor

1997-06-13

1999-12-28

Ulm, John

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

4352523, 4353201, 530380, 536 235, C07K 14705, C12N 1512

Patent

active

060080124

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to a novel human somatostatin-like receptor, isolated nucleic acids encoding same, recombinant host cell transformed with DNA encoding said receptor and to uses of the expressed receptor and nucleic acid sequences in drug screening and development as well as in therapeutic and diagnostic applications.


BACKGROUND OF THE INVENTION

Somatostatin (SST) is produced endogenously as two bioactive peptides which act on numerous target cells notably in the brain, pancreas, gastoinestinal tract, pituitary, adrenals and thyroid to regulate cell processes such sa neurotransmission, glandular secretion, smooth muscle contractility and cell proliferation (Reichlin, S., N. Eng. J. Med., 309:1495-1501 and 1556-1563 (1983)). Thus somatostatin can function as a neurotransmitter as well as a hormone. Its hormonal effects include suppression of release of many pituitary, pancreatic and gastrointestinal hormones, e.g., human growth hormone. The cellular actions of somatostatin are mediated by cell surface receptors (SSTRs), which transduce their intracellular signals via G protein-coupled pathways.
Somatostatin binds to a family of structurally-related proteins. Presently there are five known somatostatin receptor subtypes,designated SSTR1-5 (Yamada et al., Proc. Natl. Acad. Sci., 89:251-255 (1992), Yamada et al., Biochem. Biophys. Res. Comm., 195:844-852 (1993) and Patel et al., Biochem. Biophys. Res. Comm., 198:605-612 (1994)).
This invention thus provides a novel receptor of the human somatostatin subtype. The DNAs of this invention, such as the specific sequences disclosed herein, are useful in that they encode the genetic information required for expression of this novel class of somatostatin receptors. Additionally, the sequences may be used as probes in order to isolated and identify addition members of the family, type and/or subtype as well as forming the basis of antisense therapy for disease conditions which are characterized by atypical expression of the somatostatin gene. The novel protein is itself useful as a therapeutic, a diagnostic agent (e.g., antibodies that specifically bind to such protein), and as a component in a screening system for drugs which are antagonists or agonists of such receptor activity. These and additional uses for the reagents described herein will be come apparent to those of ordinary skill in the art upon reading this specification.


SUMMARY OF THE INVENTION

This invention provides isolated nucleic acid molecules encoding a human somatostatin-like receptor, including mRNAs, DNAs, cDNAs as well as antisense analogs thereof and biologically active and diagnostically or therapeutically useful fragments thereof.
This invention also provides recombinant vectors, such as cloning and expression plasmids useful as reagents in the recombinant production of human somatostatin-like proteins or peptides, as well as recombinant prokaryotic and/or eukaryotic host cells comprising human somatostatin-like nucleic acid sequence.
This invention also provides methods of identifying ligands capable of binding to human somatostatin-like receptors by measuring the binding of the ligand to be identified relative to known ligands.
This invention also provides a process for preparing a somatostatin receptor which comprises culturing recombinant prokaryotic and/or eukaryotic host cells, containing human somatostatin-like nucleic acid sequence, under conditions promoting expression of said receptor. Another related aspect of this invention is an isolated human somatostatin receptor protein and antibodies that are directed (i.e., bind) to the receptor protein of the instant invention.
This invention also provides methods for screening drugs to identify such drugs which interact with and bind to human somatostatin-like receptors. The receptors may be in isolated form (e.g., as a membrane preparation) or may be expressed on the surface of recombinant host cells. Regardless of the form of the receptor, a plurality of candidate drugs are contacted with the receptor un

REFERENCES:
Kolakowski et al., "Characterization of a human gene related to genes encoding somatostatin receptors," FEBS Letters 398, pp. 253-258 (1996).
Rohrer et al., "Cloning and Characterization of a Fourth Human Somatostatin Receptor", Proceedings of the National Academy of Science, vol. 90, pp. 4196-4200 (1993).
Yamada et al., "Cloning and Functional Characterization of a Family of Human and Mouse Somatostatin Receptors Expressed in Brain, Gastrointestinal Tract and Kidney", Proceedings of the National Academy of Science, vol. 89, pp. 251-255 (1992).

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