INTERLEUKIN 1 REGULATION OF BRADYKININ RECEPTORS

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$49,611.00
Award Year:
1989
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Award Id:
11121
Agency Tracking Number:
11121
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
6200 Freeport Ctr, Baltimore, MD, 21224
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
() -
Business Contact:
() -
Research Institution:
n/a
Abstract
BRADYKININ (BK), SYNTHESIZED FOLLOWING MANY PATHOLOGICAL INSULTS, CAUSES SMOOTH MUSCLE CONTRACTION, INCREASED VASCULAR PERMEABILITY, AND STIMULATION OF NEURONAL PAIN RECEPTORS, ACTIONS GENERALLY MEDIATED THROUGH B2 RECEPTORS. IN SOME ANIMAL DISEASE MODELS, THERE APPEARS IN VASCULAR SMOOTH MUSCLE A DIFFERENT RECEPTOR ON WHICH DES-ARG(9)-BK IS AN AGONIST. EVIDENCE SUGGESTS THAT INTERLEUKIN-1 (IL-1) IS RESPONSIBLE FOR INDUCING THESE B1 RECEPTORS. SIMILARLY, IN SEVERAL MODELS OF HUMAN PATHOLOGY AND IN TISSUE FROM PATIENTS WITH DISEASES THOUGHT TO BE MEDIATED BY OVERPRODUCTION OF IL-1, BK RESPONSIVENESS IS DRAMATICALLY INCREASED. MOREOVER, IF HEALTHY TISSUE IS TREATED WITH IL-1, RESPONSES TO BK INCREASE. THUR, IL-1 SENSITIZES TISSUES TO THE ACTIONOF BK AND MAY DO SO THROUGH INDUCTION OF B1 RECEPTORS. BK ANTAGONISTS BASED ON SCREENS OF B2 RECEPTORS ARE CURRENTLY BEING DEVELOPED. THE B1 RECEPTOR, HOWEVER, MAY BE MORE IMPORTANT IN SEVERAL INFLAMMATORY DISEASES. ANOTHER POTENTIALLY VERY IMPORTANT APPROACH MAY BE DEVELOPMENT OF AN IL-1 INHIBITOR TO TREAT INFLAMMATORY DISEASES. PHASE I RESEARCH WILL ELUCIDATE IL-1'S ROLE IN INCREASING TISSUE RESPONSIVENESS TO BK AND IN INDUCING B1 RECEPTORS. A PROGRAM TO IDENTIFY NONPEPTIDE IL-1 ANTAGONISTS/INHIBITORSWILL BE DEVELOPED. METHODS WILL INCLUDE BIOCHEMICAL AND ISOLATED TISSUE STUDIES, AS WELL AS WHOLE ANIMAL EXPERIMENTS. AGENTS HAVING IL-1 INHIBITORY ACTIVITY WILL PROVIDE LEAD STRUCTURES FOR INITIATING SYNTHETIC EFFORTS IN PHASE II.

* information listed above is at the time of submission.

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