neurologic disorders
Neurotransmission
Receptors
Neurotransmitter receptors are protein complexes that span the cell membrane. Their nature determines whether a given neurotransmitter is excitatory or inhibitory. Receptors that are continuously stimulated by neurotransmitters or drugs become desensitized (downregulated); those that are not stimulated by their neurotransmitter or are chronically blocked by drugs become supersensitive (upregulated). Downregulation or upregulation of receptors strongly influences the development of tolerance and physical dependence. These concepts are particularly important in organ or tissue transplantation, in which denervation deprives receptors of their neurotransmitter; as a result, transplanted organs may become overly sensitive to neural stimulation. Withdrawal symptoms can be explained at least in part by a rebound phenomenon due to altered receptor affinity or density. Most neurotransmitters interact primarily with postsynaptic receptors, but some receptors are located on presynaptic neurons, providing fine control of neurotransmitter release. One family of receptors, termed ionotropic receptors (eg,N-methyl-d-glutamate, kinate-quisqualate, nicotinic acetylcholine,glycine, and gamma-aminobutyric acid [GABA] receptors), consist of ion channels that open when bound to the neurotransmitter and effect a very rapid response. In the other family, termed metabotropic receptors (eg, serotonin, alpha- and beta-adrenergic, and dopaminergic receptors), neurotransmitters interact with G proteins and activate another molecule (second messenger such as cAMP) that catalyzes a chain of events through protein phosphorylation, calcium mobilization, or both; cellular changes mediated by second messengers are slower and permit finer tuning of the rapid ionotropic neurotransmitter response. Far more neurotransmitters activate specific receptors than second messengers. 