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High-probability grants
According to our matching algorithm, Roger G Pertwee is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 1998 — 2000 |
Pertwee, Roger Guy |
P01Activity Code Description:
For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Endogenous Cannabinoids and Cb1 Receptors--Structure/Activity/Tolerance Study @ Virginia Commonwealth University
Cannabinoid receptors (CB/1 and CB/2) and endogenous agonists for these receptors (anandamide and 2-arachi-donoyl glycerol) together form the "endogenous cannabinoid system". As stable analogs of endogenous cannabinoids should have clinical applications and/or serve as powerful experimental tools with which to explore the physiology of this system, part of the project will be directed at developing such agents. This will be achieved by using analogs specially designed and synthesized for this project, to explore the structural features of endogenous cannabinoids that govern their potency in systems that contain the cannabinoid receptor type found on central and peripheral neurons (CB/1). The project will also establish the structural features of endogenous cannabinoid analogs that determine their efficacy at CB/1 receptors and compare these with those determining their affinity for CB/1 receptors. One practical outcome of this exercise will be the development of endogenous cannabinoid analogs whose potencies depend mainly on efficacy. Such compounds are expected to have more consistent pharmacological properties in different biological systems than agonists whose potency depends mainly on affinity. The other main objective of this project is to determine the basis of cannabinoid tolerance by establishing the extent to which tolerance induced by in vivo administration of a CB/1 receptor agonist can be attributed to decreases in CB/1 receptor affinity, CB/1 receptor density/internalization and/or CB/1 coupling efficiency. Guinea-pig or mouse isolated tissue preparations that contain CB/1 receptors on nerve terminals will be used as functional bioassay systems to provide potency values and to investigate tolerance, induced by in vivo cannabinoid treatment. Binding assays will be used to determine CB/1 receptor affinity values and also to detect any changes in cannabinoid receptor affinity or density associated with tolerance. It is intended to monitor CB/1 receptor coupling efficiency in tolerant and non- tolerant tissues by measuring the ability of CB/1 receptor agonist to enhance GTPgammaS binding and to look for receptor internalization by immunofluorescence confocal microscopy.
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0.943 |