Ghrelin

Ghrelin in humans

Known actions of ghrelin on various target tissues (source).

Ghrelin is a vertebrate peptide hormone that has been most heavily studied for its role as a signalling molecule that is made in the gastrointestinal tract and which can modulate the behavior of ghrelin receptors on neurons, both in the peripheral and the central nervous system. One of the most well-studied functions of ghrelin in the nervous system is for regulation of eating behavior. Soon after its discovery (2001), exogenous ghrelin was shown to increase food consumption in humans.

GOAT

acylation of ghrelin by GOAT (source)

One of the interesting features of ghrelin as a peptide hormone is that acylation of the ghrelin peptide is required for binding of the hormone to its receptor, GHSR1.

The acylation of ghrelin seems to be regulated. An hypothesis was proposed (2009) that ghrelin might function as part of a regulatory system for supporting and enhancing food consumption under conditions where high-energy sources are available in the environment.

How ghrelin acts through binding to the GHSR1 G Protein-coupled receptor is being studied in both peripheral sensory neurons and neurons of the CNS. Some of ghrelin’s action to increase feeding behavior might be due to blockage of appetite suppressing signals that reach the brain by way of sensory neurons that transmit signals from the gut.

In addition to effects on neurons of the peripheral nervous system, ghrelin influences the activity of CNS neurons such as populations of neurons in the hypothalamus that regulate feeding behavior (2015a). In a study of hypothalamic neurons (2015), GHSR1 was shown to inhibit pre-synaptic calcium channel activity and inhibit GABA release. It is hypothesized that this could contribute to ghrelin’s ability to regulate parts of the hypothalamus that are involved in the regulation of eating behavior.

Ghrelin receptors in other parts of the brain in addition to the hypothalamus seem to be involved in the regulation of learned eating behaviors and calorie-rich food seeking behaviors. Since 1) the GHSR1 receptor has high levels of activation even in the absence of ghrelin binding (2009) and 2) GHSR1 can form complexes with other receptors (2013), it is not clear that all the functions of ghrelin receptors in the brain rely on the transport of ghrelin across the blood-brain barrier. Neurons in various brain regions such as the mesolimbic reward system display altered electrical activity in response to administered ghrelin under conditions where GHSR1 receptors interact in complex ways with other neurotransmitter systems (2016).

hypothalamus

Model for action of ghrelin in the CNS (source)

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About johnwschmidt

Exploring medical physiology.
This entry was posted in brain, signal transduction. Bookmark the permalink.

One Response to Ghrelin

  1. Pingback: Circadian Pacemaker | medicalneurophys

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