Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1998-03-16
2002-04-02
Kunz, Gary L. (Department: 1647)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007100, C435S007210, C435S069100, C530S350000
Reexamination Certificate
active
06365360
ABSTRACT:
BACKGROUND OF THE INVENTION
PGI
2
causes relaxation of arterial smooth muscle and inhibition of platelet aggregation, degranulation and shape change and is, therefore, thought to be important in maintaining vascular homeostasis. Other potential roles for PGI
2
are not well established but include regulation of renal blood flow, renin release and glomerular filtration rate in the kidney cortex, modulation of neurotransmitter release in the heart and stimulation of secretion in the stomach and large intestine. In common with the other prostaglandins, PGI
2
in also involved in the inflammatory response elicting hyperaemia, edema, hyperanalgesia and pyrexia primarily through its role as a vasodilator.
The physiological actions of prostaglandin (PG)I
2
are mediated through interaction with the prostaglandin IP receptor. The known distribution of IP receptors is reflective of the physiological actions of PGI
2
. They have been extensively characterized by radioligand binding studies in platelets from many species including human and identified in pharmacological studies as present in coronary, pulmonary, renal and several other arterial preparations as well as the heart. IP receptors may also be present in myometrium, penile erectile tissue and the iris sphincter muscle and have been reported in the NCB-20 and NG 108-15 neuronal hybrid cell lines and the mouse mastocytoma P-815 cell line.
Functional activities of the IP receptor have been studied using tissue preparations such as arterial smooth muscle and cell based assays using platelets. The above methods for studying IP receptor activities have several disadvantages in that they require preparations containing several different but related receptor populations, with different ligand binding properties, making measurements of absolute potency and selectivity very difficult. In addition, tissues contain varying levels of IP receptor and since tissue samples are required, compounds cannot satisfactorily be tested as effectors of the human IP receptor.
SUMMARY OF THE INVENTION
A novel prostaglandin receptor protein termed IP has been identified from human cells. A DNA molecule encoding the full length IP protein has been isolated and purified, and the nucleotide sequence has been determined. The IP encoding DNA has been cloned into expression vectors and these expression vectors, when introduced into recombinant host cells, cause the recombinant host cells to express a functional IP receptor protein. The novel IP protein, the IP-encoding DNA, the expression vectors and recombinant host cells expressing recombinant IP are useful in the identification of modulators of IP receptor activity.
A method of identifying IP receptor modulators is also disclosed which utilizes the recombinant IP expressing host cells. Modulators of IP activity are useful for the treatment of prostaglandin-related diseases and for modulating the effects of prostaglandins on the IP receptor.
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Abramovitz Mark
Boie Yves
Grygorczyk Richard
Metters Kathleen
Rushmore Thomas H.
Hand J. Mark
Kunz Gary L.
Landsman Robert S.
Merck Frosst Canada & Co.
Tribble Jack L.
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