Colonic Fluid and Electrolyte Transport 2022: An Update.

Colonic epithelial cells are responsible for maintaining a delicate balance between luminal secretion and the absorption of fluids and ions. This review aims to discuss and update the model of colonic electrolyte secretion and absorption via the cystic fibrosis transmembrane regulator (CFTR), epithelial sodium channel (ENaC), Na-K-Cl cotransporters (NKCC1 and 2), Na-H exchangers (NHE1-4), colonic H,KATPase, and several other key components involved in multi-level transepithelial ion transport. Developments in our understanding of the activity, regulation, localization, and relationships of these ion transporters and their interactions have helped forge a more robust understanding of colonic ion movement that accounts for the colonic epithelium's role in mucosal pH modulation, the setting of osmotic gradients pivotal for fluid retention and secretion, and cell death regulation.

3D Bioprinting of Vascularized Tissues for and Applications.

With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal.

A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter.

The serotonin transporter (SERT) is the primary target for the selective serotonin reuptake inhibitors (SSRIs). However, the structural basis for the extraordinarily high binding affinity of the widely prescribed SSRI, paroxetine, to human SERT (hSERT) has not yet been fully elucidated. Our previous findings unveiled a plausible ambiguity in paroxetine's binding orientations that may constitute an integral component of this SSRI's high affinity for hSERT.

Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics.

The serotonin transporter (SERT) is one of the primary targets for medications to treat neuropsychiatric disorders and functions by exploiting pre-existing ion gradients of Na, Cl, and K to translocate serotonin from the synaptic cleft into the presynaptic neuron. Although recent hSERT crystal structures represent a milestone for structure-function analyses of mammalian neurotransmitter:sodium symporters, they are all derived from thermostabilized but transport-deficient constructs. Two of these structures are in complex with paroxetine, the most potent selective serotonin reuptake inhibitor known.

Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.

The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial.

ATP dependence of Na+-driven Cl-HCO3 exchange in squid axons.

Squid giant axons recover from acid loads by activating a Na(+)-driven Cl-HCO(3) exchanger. We internally dialyzed axons to an intracellular pH (pH( i )) of 6.7, halted dialysis and monitored the pH(i) recovery (increase) in the presence of ATP or other nucleotides, using cyanide to block oxidative phosphorylation.

Cloning of a Na+-driven Cl/HCO3 exchanger from squid giant fiber lobe.

We extracted RNA from the giant fiber lobe (GFL) of the squid Loligo pealei and performed PCR with degenerate primers that were based on highly conserved regions of Na+-coupled HCO3- transporters. This approach yielded a novel, 290-bp sequence related to the bicarbonate transporter superfamily. Using an L.