Table A4.1 Superfamilies of receptors.Superfamily General notes concerning their action
Type 1 Opens ion channels.
Type 2 Binding causes a conformational change, which results in the attraction of a
G-protein in the cytoplasm to an intracellular binding domain of the receptor
molecule. This may either result in the opening or closing of an ion channel or the
inhibition or activation of an enzyme.Type 3 It is believed that the binding of a ligand to this type of receptor causes the receptor
to dimerize. This is thought to result in conformational changes that cause the
autophosphorylation of various tyrosine residues in the intracellular domain.
These phosphorylated tyrosine sites act as high affinity binding sites for specific
intercellular proteins.
Type 4 The members of this family occur in the nucleus of the cell. The N-terminal side of
the receptor protein appears to control gene transcription.cholinergic receptors (nAChR). Similarly muscarine will only bind to muscari-
nic cholinergic receptors (mAChR). However, it is possible to differentiate be-
tween different types of receptor within a sub-type. For example, three different
types of muscarinic cholinergic receptor have been detected and a further two
predicted from a study of the genes that code for this type of receptor. These five
mAChR receptors are classified as mn, wherenis an integer form 1 to 5 inclusive.
Similar classifications are used for other receptors. For example, adrenocep-
tors are classified asaandbsub-types. These sub-types are further classified
according to the nature of their exogenous ligands. The various types are
distinguished by the use of subscript numbers.
The forces binding ligands to receptors covers the full spectrum of chemical
bonding, namely covalent bonding, ionic bonding, dipole–dipole interactions of
all types including hydrogen bonding, charge-transfer bonding, hydrophobic
bonding and van der Waals’ forces. The bonds between the ligand and the
receptor are assumed to be formed spontaneously when the ligand reaches the
appropriate distance from its receptor for bond formation.
The binding of many drugs to their receptors is by weak reversible inter-
actions.
drugþreceptorÐdrugreceptor (A4:1)
This means that the binding of a drug to its receptor is concentration
dependent.
As the concentration of the ligand in the extracellular fluid increases, equilib-
rium (A4.1) will move to the right and the drug will bind to the receptor.
APPENDIX 4 RECEPTORS 247