The present invention relates to novel identified polynucleotides, polypeptides
encoded by them and to the use of such polynucleotides and polypeptides, and to
their production. More particularly, the polynucleotides and polypeptides of the
present invention relate to the G-protein coupled receptor family, referred to
as IGS4-family. The invention also relates to inhibiting or activating the action
of such polynucleotides and polypeptides, to a vector containing said polynucleotides,
a host cell containing such vector and transgenic animals where the IGS4-gene is
either overexpressed, misexpressed, underexpressed or suppressed (knock-out animals).
The invention further relates to a method for screening compounds capable to act
as an agonist or an antagonist of said G-protein coupled receptor family IGS4 and
the use of IGS4 polypeptides and polynucleotides and agonists or antagonists to
the IGS4 receptor family in the treatment of PNS, psychiatric and CNS disorders,
including schizophrenia, episodic paroxysmal anxiety (EPA) disorders such as obsessive
compulsive disorder (OCD), post traumatic stress disorder (PTSD), phobia and panic,
major depressive disorder, bipolar disorder, Parkinson's disease, general anxiety
disorder, autism, delirium, multiple sclerosis, Alzheimer disease/dementia and
other neurodegenerative diseases, severe mental retardation, dyskinesias, Huntington's
disease, Tourett's syndrome, tics, tremor, dystonia, spasms, anorexia, bulimia,
stroke, addiction/dependency/craving, sleep disorder, epilepsy, migraine; attention
deficit/hyperactivity disorder (ADHD); cardiovascular diseases, including heart
failure, angina pectoris, arrhythmias, myocardial infarction, cardiac hypertrophy,
hypotension, hypertension e.g. essential hypertension, renal hypertension, or pulmonary
hypertension, thrombosis, arteriosclerosis, cerebral vasospasm, subarachnoid hemorrhage,
cerebral ischemia, cerebral infarction, peripheral vascular disease, Raynaud's
disease, kidney disease—e.g. renal failure; dyslipidemias; obesity; emesis;
gastrointestinal disorders, including irritable bowel syndrome (IBS), inflammatory
bowel disease (IBD), gastroesophagal reflux disease (GERD), motility disorders
and conditions of delayed gastric emptying, such as post operative or diabetic
gastroparesis, and diabetes, ulcers—e.g. gastric ulcer; diarrhoea; other
diseases including osteoporosis; inflammations; infections such as bacterial, fungal,
protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2;
pain; cancers; chemotherapy induced injury; tumor invasion; immune disorders; urinary
retention; asthma; allergies; arthritis; benign prostatic hypertrophy; endotoxin
shock; sepsis; complication of diabetes mellitus; and gynaecological disorders,
among others and diagnostic assays for such conditions. Preferred uses of the invention
relate to disorders of the nervous system, including the central nervous system
(CNS) and the peripheral nervous system (PNS), disorders of the gastrointestinal
system and/or of the cardiovascular system and/or of skeletal muscle and/or of
the thyroid, and/or also to lung diseases, immunological diseases and disorders
of the genitourinary system. The invention also relates to the identification of
the cognate ligand of the IGS4 polypeptides of the invention. High affinity binding
to said IGS4 polypeptides is found for the neuropeptides known as neuromedin U.