Metabotropi

Metabotropi, or metabotropic receptors, are a class of cell-surface receptors that transduce signals through intracellular second messenger pathways rather than forming an ion channel. The most prominent metabotropic receptors are the G protein-coupled receptors (GPCRs), which cross the membrane seven times. When a ligand binds, the receptor activates heterotrimeric G proteins (Gs, Gi/o, or Gq/11), which in turn regulate enzymes such as adenylyl cyclase or phospholipase C. This leads to the production of second messengers such as cyclic AMP (cAMP) or inositol trisphosphate and diacylglycerol (IP3/DAG), which modulate a wide range of targets, including ion channels, enzymes, and transcription factors. The signaling cascades typically produce slower, but longer-lasting, effects compared with ionotropic receptors.

Metabotropic receptors have diverse roles in the nervous system and beyond, including regulation of synaptic transmission, neuronal excitability, plasticity, mood, perception, and autonomic function. Well-known examples include muscarinic acetylcholine receptors, adrenergic receptors, dopamine receptors, serotonin receptors, and the metabotropic glutamate receptors (mGluRs). GABA-B receptors are another well-studied group of metabotropic receptors.

Pharmacologically, metabotropic receptors are important drug targets. They are targeted by drugs for cardiovascular disease (e.g., beta-adrenergic blockers), psychiatric and neurological disorders, and pain. Persistent receptor activity can be modulated by allosteric modulators, biased agonists, and mechanisms of desensitization and internalization involving beta-arrestins.

In contrast to ionotropic receptors, metabotropic receptors do not form an open ion channel, but initiate signaling cascades that shape cellular responses over seconds to minutes or longer.