Effects of age, postmortem delay and storage time on receptor-mediated activation of G-proteins in human brain

The influence of age, postmortem delay and freezing storage period on receptor-mediated G-protein activity was quantified in cortical membranes from 34 healthy subjects. Concentration-response curves of the [S-35]GTPgammaS binding stimulation by agonists for alpha(2)-adrenoceptors (UK14304), mu-opioid (DAMGO), 5-HT1A (8-OH-DPAT), GABA(B) (baclofen) and muscarinic (carbachol) receptors were analyzed. Immunoreactivities of G(alpha)-protein subunits were also determined. Basal binding and UK14304, 8-OH-DPAT, and baclofen potency to stimulate [S-35]GTPgammaS binding decreased with aging (1-88 years) without changes of efficacy. DAMGO-mediated stimulation increased both in potency and efficacy with aging. A negative correlation between age and immunoreactivity was observed for G(alphai1/2)- but not for G(alphai3)-, G(alpha0)-, and G(alphas)-proteins. Neither [S-35]GTPgammaS binding nor G.-proteins changed with the postmortem delay (8-92 h). Basal [S-35]GTPgammaS binding decreased with the sample storage period (1-85 months). A careful match between cases and controls should be taken into account when designing signal transduction studies in human disorders, specially for variables such as age and storage period. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.