Thursday, April 20, 2017

Serotonin-binding protein and LSD

Serotonin-binding protein

A ~50 kDa protein that binds serotonin was first identified in 1974. It was discovered by passing all of the soluble extracts of a cell over a 5-HT affinity column, and then eluting the column with 5-HT. The protein was stored with 5-HT to prevent degradation.

Serotonin-binding protein is expressed in enteric and central serotonergic neurons, including enterochromaffin cells, the nuclei raphe dorsalis, centralis superior, raphe medianus, raphe magnus, raphe obscurus, and raphe pallidus. Also, dense staining with antibodies to serotonin-binding protein was found in the supraependymal plexus lining the ventricular surfaces.

Serotonin-binding protein and LSD

In 1977, Shih and colleagues performed spectroscopic analysis of free LSD and LSD bound to serotonin-binding protein. Free LSD exhibited max fluorescence at 435 nm with excitation at 330 nm, while serotonin-binding-protein-bound-LSD shifted its fluorescence and excitation maximum to 465 nm and 375 nm. These results suggest that the interaction between LSD and serotonin-binding-protein caused a delocalization of the molecular orbital electrons and thereby lengthened the electronic conjugation of the drug molecule.

Figure 2 below shows the excitation (330 nm) and emission (435 nm) wavelengths of free LSD.


Figure 3 shows the excitation (375 nm) and emission (465 nm) wavelengths for protein-bound-LSD.


An increase in the absorption and emission wavelengths was also observed when bovine serum albumin (BSA) was mixed with LSD, as shown in the next figure. Peak 1 is the fluorescence of BSA. Peak 2 is shifted towards longer wavelengths, and represents the BSA-LSD complex.


Generally, a shift of the absorbance towards longer wavelengths can be accomplished by adding Sulfur, Nitrogen, or Oxygen to a molecule, which increases the number of loosely bound electrons. Serotonin-binding-protein and other proteins contain lone pairs of electrons from S, N, and O that can add to the pi-electron system of the LSD molecule, thus modifying its spectra absorbance.


Reference

Shih J. C. and J. Rho (1977). The specific interaction between LSD and serotonin-binding protein. Research communications in chemical pathology and pharmacology 16, 637-647.

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