metabotrope

Metabotropic receptors, commonly referred to as metabotropes, are a class of cell-surface receptors that mediate neurotransmission through intracellular signaling cascades rather than forming an ion channel. They typically produce slower, longer-lasting effects compared with ionotropic receptors, modulating cellular activity over seconds to hours.

Most metabotropic receptors belong to the seven-transmembrane G protein-coupled receptor (GPCR) superfamily. Upon ligand binding, they activate heterotrimeric G proteins (such as Gs, Gi/o, or Gq/11) or engage other pathways like β-arrestin signaling. This activation alters intracellular second messengers, including cyclic AMP, inositol triphosphate, diacylglycerol, and calcium, thereby modulating ion channels, enzyme activity, and gene expression.

Examples of metabotropic receptors include metabotropic glutamate receptors (mGluRs), muscarinic acetylcholine receptors, various dopamine receptors (D1-like and D2-like), and many serotonin and adrenergic receptor subtypes. Through these receptors, neurons can regulate synaptic transmission, neuronal excitability, and synaptic plasticity, influencing processes such as learning, memory, and mood.

Clinical and pharmacological relevance: metabotropic receptors are important drug targets in neurology and psychiatry. Their signaling complexity and tissue-specific effects can pose challenges for therapeutic design, but strategies such as allosteric modulators and biased agonism aim to achieve more selective outcomes with fewer side effects.