Anesthesia & Clinical Research
Open Access

Abstract

Effect of n-Alkanols on G-Protein a Subunits

Srinivas Pentyala, Kavita Tanguturi, Anas Sawas, Amulya Veerraju, Sandeep Annam, Laura Cipp and Mario Rebecchi

Guanine nucleotide binding (G)-proteins are GTP-driven allosteric proteins consisting of a single ? subunit and a ? and ? heterodimer. G? subunits function as on/off switches based on the occupancy of the nucleotide-binding site, GTP or GDP, such that any alteration in nucleotide exchange modulates signal output. Our previous work has shown that haloalkanes and ethers inhibit GDP/GTP exchange on ?i1, ?i2 and ?i3 subunits, but not the closely related ao. To test whether individual G-protein sensitivity correlates with n-alkanols potency and hydrophobicity, we studied the effects of n-alkanols of varied chain lengths on GDP/GTP exchange by G? subunits. n-alkanols (ethanol, butanol, pentanol, hexanol, heptanol, octanol and nonanol) showed differential effects on guanine nucleotide exchange by G?i1, G?i2 and G?o. Based on our observations, we conclude that n-alkanols interact and modulate the activity of the G-? subunits to different extent, thereby uncoupling pathways known to modulate neuronal excitation.