Biomedical Engineering Reference
In-Depth Information
muscle cells and perivascular sympathetic neurons) as well as circulating red blood
capsules using various mechanisms: vesicular exocytosis, ATP-binding cassette
(ABC) transporters, and connexin- and pannexin-based channels.
7.9.3.1
Vesicular Exocytosis
Exocytosis is the release of soluble intracellular molecules into the extracellular
space. For example, perivascular sympathetic nerve terminals liberate from synaptic
vesicles the neurotransmitter noradrenaline as well as ATP that targets
-adrenergic
receptors of postjunctional membranes of innervated vascular smooth myocytes and
primes vasoconstriction. Endothelial cells may also release ATP from stores via
exocytosis during changes in blood flow.
Neurons secrete many neurotransmitters, such as catecholamines (dopamine and
noradrenaline), amines (acetylcholine, serotonin, and histamine), and amino acids
(glutamate, glycine, and GABA). Vesicular transporters are generally non-selective:
vesicular monoamine transporters VMAT1 and VMAT2 (SLC18a1-SLC18a2) carry
serotonin, noradrenaline, and dopamine; vesicular inhibitory amino acid transporter
(VIAAT, or SLC32a1) conveys GABA and glycine. However, vesicular acetyl-
choline transporter (VAChT, or SLC18a3) transports only acetylcholine; glutamate
transporters VGluT1 to VGluT3 (SLC17a6-SLC17a8) are selective for glutamate.
Vesicular nucleotide transporter (VNuT, or SLC17a9) is a secretory vesicle
protein responsible for the vesicular storage of ATP as well as ADP and GTP, using
ATP and proton via vacuolar ATPase to create an electrochemical potential and a
pH gradient across the vesicular membrane, and subsequent exocytosis [ 693 ]. It
also carries divalent cation, such as Ca 2 + and Mg 2 + , when ATP is present [ 694 ].
Extracellular ATP and ATP-containing specialized vesicles can be detected
in most non-excitatory tissues. Vascular endothelial cells may store ATP bound
to peptides in vesicles [ 695 ]. Messenger ATP can be secreted from endothelial
cells as well as airway epithelial cells, among others, which are subjected to
mechanical stresses [ 685 ]. Aortic endothelial and smooth muscle cells stimulated by
thrombin release ATP messenger. Endothelial cells release nucleotides in response
to bradykinin, acetylcholine, and serotonin [ 685 ].
Basal ATP release by resting cells enables autocrine activation of nucleotide P2Y
receptor, hence basal activity of some proteins such as the calcium- and cAMP-
sensitive chloride (CFTR) channels in airway epithelial cells, vascular smooth
muscle and endothelial cells, red blood capsules, and platelets.
α
7.9.3.2
ABC Transporters
ATP-binding cassette transporters use the energy of ATP hydrolysis to support
the motion across the plasma membrane of macromolecules such as cholesterol
(Vol. 3 - Chap. 4. Membrane Compound Carriers). Cystic fibrosis transmembrane
conductance regulator (CFTR, ABC35, or ABCc7), multidrug resistance gene
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