Cerebrovascular Activity of Peptides Generated by Central Nervous System

Peptides and Neuropeptides: Definitions

Peptides are biologically occurring short chains of amino acid monomers linked by amide bonds. Arbitrarily, peptides are distinguished from proteins on the basis of size: they contain approximately 50 or fewer amino acids.

Neuropeptides are peptides used by neurons to communicate with each other . Nerve cells communicate with each other through two mechanisms: (1) fast synaptic transmission through fast-acting neurotransmitter (e.g., glutamate = excitatory; gamma-aminobutyric acid = inhibitory), which achieves effects within 1 ms, and (2) slow synaptic transmission through peptide neurotransmitters that influence the activity of the brain over hundreds of milliseconds to minutes .

Some peptides of cerebral origin are not stricto sensu defined as neuropeptide based on the cell types that release and respond to the molecule:

• Neuropeptides are secreted from neuronal cells and signal to neighboring cells (primarily neurons).

• Peptides of cerebral origin are secreted or act on cells other than neurons, mainly on the cells of the cerebral vasculature, like endothelial cell or smooth muscle cell.

Functions of Peptides and Neuropeptides

Neuropeptides modulate neuronal communication by acting on cell surface receptors. This latter process is mediated through a more complicated sequence of biochemical steps: neuropeptides act mainly on G-protein-coupled receptors, which activate an intracellular cascade of molecular enzymatic events, followed by cellular responses. Subsequently, this response occurs in a time span considerably longer than that of low-molecular-weight fast neurotransmitters .

Neuropeptides control the efficacy of fast synaptic transmission by regulating the efficiency of neurotransmitter release from presynaptic terminals and by regulating the efficiency with which fast-acting neurotransmitters produce their effects on postsynaptic receptors . Peptides have several effects on cerebral blood flow, synaptogenesis, glial cells morphology, and gene expression, so subsequently on brain functions like analgesia, food intake, metabolism, reproduction, social behaviors, learning and memory, etc.

Physiology

Endothelins are 21-amino acid peptides that constrict blood vessels and raise blood pressure. Their name derived from the fact that they were first identified in cultured endothelial cells. Endothelins are the most potent vasoconstrictors known. In a healthy individual, a balance between vasoconstriction and vasodilation is maintained by endothelin and other vasoconstrictors on the one hand, and nitric oxide, prostacyclin, and other vasodilators on the other .

There are three isoforms of endothelin: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3), but ET-1 is the only isoform produced by endothelial cells. There are three main endothelin receptors: ET(A)-receptor, ET(B)-receptor, and ET(C)-receptor . The varying regions of expression of endothelin peptides and receptors implicate its involvement in a wide variety of physiological processes in the body.