Partial agonists, inverse agonists and spare receptors

del Castillo-Katz mechanism

full agonist

able to elicit a maximal tissue response

partial agonist

cannot elicit maximal response, no matter that concentration

difference between full and partial agonist action

both cause conformational change, full agonist stabilises

Slow Channel Congenital Myasthenic Syndrome

prolonged endplate currents

constitutively active receptors

activate in the absence of agonist

ligand binding to R and R*

if L only binds to inactive - encourages formation of inactive receptors - inverse agonist/negative antagonist
if L only combines with R*, has reverse reaction - conventional agonist
if L has equal affinity for R and R*, no effect on fraction of receptors in active state - reversible competitive antagonist

desensitisation of receptor

can isomerise into inactive, desensitised state
G protein coupled receptors can be phosphorylated - can be followed by loss of receptors from cell surface

spare receptors

extra to ensure maximal response reached