Introducing the brain: many neuropeptides signal (Introduction)

by David Turell , Friday, November 17, 2023, 15:24 (162 days ago) @ David Turell

A plethora of different types do signaling:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/17_november_2023/41...

"CommunicatIon between neurons in the brain involves the release of either fast (for example, glutamate, γ-aminobutyric acid) or slow neurotransmitters (for example, catecholamines, histamine) from the presynaptic terminal, alone or together with neuromodulators. Fast neurotransmitters induce ion currents in the postsynaptic neuron. By contrast, slow neurotransmitters and neuromodulators act on metabotropic G protein–coupled receptors (GPCRs) in the postsynaptic membrane to trigger intracellular second messenger cascades. Neuropeptides are a superfamily of neuromodulators—more than 100 have been identified.

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"Wang et al. (1) describe GPCR-activation–based sensors (GRABs) that can track neuropeptide action in vivo. Such GRABs have the potential to provide new information on physiological processes (2) and the role of GPCRs in brain diseases.

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"Accordingly, the type of neurotransmitter used would determine whether that neuron inhibited or activated its partner postsynaptic neuron or neurons. Fast neurotransmitters are limited in number and produce almost binary (“yes” or “no” codes for neurotransmission. This communication needs continuous recalibration to optimize its strength. Neuropeptides are ideal for this role.

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"Most, if not all, synapses contain both a neurotransmitter and a neuropeptide, at least in some brain regions (6). Neuropeptide precursors (prepropeptides) can often be cleaved into alternative short fragments, each with different (or overlapping) action. Therefore, neuropeptides could produce combinatorial codes to modulate the action or prime the sensitivity of neurons to neurotransmitters. This notion is supported by the observation that neuropeptides commonly have multiple cognate GPCRs—some stimulating (through Gαq and Gas protein cascades) and some inhibiting (through Gαi and Gαo protein signaling) the postsynaptic neuron. Thus, GPCRs augment or dampen the efficacy of neurotransmitters, respectively.

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"Neuropeptides are also released by nonneuronal cells, including endocrine cells of the gastrointestinal tract and pancreas, for long-range signaling. In the pancreas, SST [somatostatin] is a marker of δ cells (14), whose activity modulates the release of both insulin and glucagon."

Comment: the complexity of signaling is shown in this article. The coordinating of signals and receptors and the modulation of those signals are markers of irreducible complexity and require design.