30th Sept - Introduction Flashcards
What is the receptor concept?
That the majority of drugs exert their effects through specific interactions with cellular macromolecules
Who first proposed the receptor concept in 1900s?
Langley and Ehrlich
What is AJ Clark’s Occupation theory (1930)?
It assumed that the intensity of the drugs effect was directly proportional to the number of receptors occupied
What did Clark, Gaddum and Schild and to AJ Clark’s occupation theory?
That agonist concentration response curves were shifted to the right with the addition of antagonist
What 2 characteristics did Ariens propose defined receptor-ligand interactions?
Affinity - the measure of binding to the receptor
Intrinsic Activity - the measure of the ability of the bound drug to evoke a cellular response
What intrinsic activity did Ariens designate to full agonists?
1
What did Stephenson define efficacy as in 1956?
A property of the agonist that would permit 2 drugs to occupy different proportions of receptors yet produce equal responses
Who showed that Stephenson’s efficacy is a tissue dependent phenomenon in the 1960s?
Furchgott
Who provided a mechanistic outline of the pathway linking hormone receptor binding in liver cells to the breakdown of glycogen to glucose?
Sutherland and Rall 1950s
Who discovered cAMP and the hormone sensitive AC?
Sutherland and Rall
What did Bimbaumer and Rodbell propose in the 1960s?
That the receptor protein that senses the hormone is seperate from AC
What does the collision coupling model propose?
That the receptors and effectors are seperate entities that can collide within the fluid-mosaic membrane
What did Orly and Schwann demonstrate in 1976?
That receptors and effectors are seperate proteins using the hybrid fusion approach
How did Orly and Schwann demonstrate that receptors and effectors are seperate proteins?
The hybrid fusion approach
Turkey erythrocytes express AC and beta adrenoceptor
Friend erythroleukaemic cells express AC
They chemically inactivated Turkey AC
Fused Turkey and Friend cells and found that beta agonist addition led to an increase in cAMP therefore receptor is seperable and mobile from the effector
What did Rodbell find when he attempted to reconstitute the signalling pathway from hormone binding to cAMP generation?
That GTP was required
How did Rodbell find that GTP was required for cAMP ?
He tried to reconstitute the signalling pathway from hormone binding to cAMP generation, using thoroughly washed membranes, ATP, hormone and Mg2+. He got highly variable results. Analysis of the ATP found that some batches were contaminated with GTP, these fave high cAMP levels and those without GTP gave little cAMP.
Who chromatagraphically purified the GTP binding protein?
Pfeuffer 1975
How did Ross and Gilman show that cyc- cells possess AC but lack the GTP binding protein?
Added into cyc- cells just a 40kda GTp binding protein and it reconsituted activity
Who found that GPCR g proteins are heterotrimeric inthe late 1980s?
Simon
