Metabotropic receptor

Metabotropic receptor is a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells.

In the nervous system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors. In contrast to the latter, metabotropic receptors do not form an ion channel pore; rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, they are a type of G protein-coupled receptor. Others are tyrosine kinases or guanylyl cyclase receptors.

What both receptor types have in common is that they are activated by specific neurotransmitters. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na⁺, K⁺, or Cl^- to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that also results in ion channel opening but must involve a range of second messenger chemicals.

Examples

This class of receptors includes the metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABA_B receptors, and most serotonin receptors, as well as receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides (Austin, 2004; Purves et al., 2001) and endocannabinoids.

Structure

The G protein-coupled receptors have seven hydrophobic transmembrane domains. Most of them are monomeric proteins, although GABA_B receptors require heterodimerization to function properly. The protein's N terminus is located on the extracellular side of the membrane and its C terminus is on the intracellular side (Purves et al., 2001).

The 7 transmembrane spanning domains, with an external amino terminus, is often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of ~ 450-550 amino acids.

Function

Metabotropic receptors have neurotransmitters as ligands, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand, also called the primary messenger, binds to the receptor, or the transducer, the latter activates a primary effector, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of molecules in turn, channels associated with these receptors take longer to open than ionotropic receptors do, and they are thus not involved in mechanisms that require quick responses (Kandel et al., 2000, p. 240). However, metabotropic receptors also remain open from seconds to minutes (Kandel et al., 2000, p. 250-251). Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds (Austin, 2004). While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread through the cell.

Metabotropic receptors can both open and close channels. They can make a membrane more excitable by closing K⁺ channels, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an action potential (Kandel et al., 2000, p. 242-243). Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic neuron (Schmitz et al., 2001). These receptors can be further classified into receptor tyrosine kinases and G protein-coupled receptors, or GPCRs (Kandel et al., 2000, p. 229)..

References

• Austin V. 2004. Fundamentals of the nervous system and nervous tissue. Pearson Education, Inc., Benjamin Cummings. From, Marieb E.N. 2004. Human Anatomy & Physiology, Sixth Edition. [1]
• Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science, 4th ed., pp.178-180. McGraw-Hill, New York (2000). ISBN 0-8385-7701-6
• Purves D., Augustine G.J., Fitzpatrick D., Katz L.C., LaMantia A.S., McNamara J.O., and Williams S.M. 2001. Neuroscience, Second Edition. Sinauer Associates, Inc. [2]
• Schmitz D, Mellor J, Nicoll RA. Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science. 9 March 2001;291(5510):1972-6. doi:10.1126/science.1057105 PMID 11239159
• Zimmerberg, B. 2002. Dopamine receptors: A representative family of metabotropic receptors. Multimedia Neuroscience Education Project. [3]