What transporters are involved in the creation of saliva?

Transporters Involved in Saliva Creation

Saliva formation depends primarily on aquaporins (AQP-3 and AQP-5), classic Na+ and Cl- ion transporters, and the cystic fibrosis transmembrane conductance regulator (CFTR).

Primary Water Transport Mechanisms

Aquaporins provide the transcellular pathway for water movement:

• AQP-5 is localized at the apical (luminal) membrane of acinar cells and mediates water outflow into the salivary duct lumen 1, 2
• AQP-3 is expressed in the basolateral membranes of both mucous and serous acinar cells and facilitates water entry from the interstitium 1
• Together, AQP-3 and AQP-5 provide the complete transcellular pathway for osmotic water flow in primary saliva formation 1
• AQP-1 is present in myoepithelial cells and capillary endothelium surrounding acini, though it plays a supporting rather than primary secretory role 3, 1

Ion Transporters and Channels

Classic electrolyte transporters generate the osmotic gradients that drive water movement:

• Na+ and Cl- ion transporters actively create electro-osmotic gradients critical for water transport 4
• Ion channels enable rapid passive movement of selected ions across cell membranes, with over 100 families identified 4
• Membrane pumps and channels actively generate transcellular transport through specific mechanisms 4

Additional Transport Proteins

Several other proteins contribute to salivary fluid secretion:

• The cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) participates in water transport 4
• Glucose transporters can be involved in water transport processes 4
• Urea transporter UT3 contributes to fluid movement 4
• Multiple Na+-solute cotransporters facilitate coordinated ion and water movement 4

Paracellular Pathway

Water also moves between cells through tight junctions:

• Tight junctions located between cells are the main routes for passive ion permeation 4
• Inflammatory mediators like histamine can alter tight junctions, allowing increased paracellular water transport 4

Neural Regulation

Saliva secretion is nerve-mediated and reflex-driven:

• Cholinergic signaling from parasympathetic nerves is largely responsible for salivary fluid secretion 5
• Sympathetic nerves and noradrenaline release additionally regulate protein content in major salivary glands 5

Clinical Significance

Dysfunction of these transporters causes xerostomia:

• AQP-1 expression in myoepithelial cells is selectively down-regulated by 38% in Sjögren's syndrome, contributing to reduced saliva production 3
• Abnormal subcellular distribution of AQP-5 occurs in xerostomia from Sjögren's syndrome and radiation 2
• AQP5-deficient mice show reduced saliva secretion under stimulation, confirming its physiological importance 2

Human salivary glands express AQP1, AQP3, and AQP5 at significant levels, with AQP4 present only at negligible amounts 1.