FUNCTIONAL AND QUANTITATIVE MEASURES OF RECEPTOR-COUPLED G-PROTEINS IN HUMAN MONONUCLEAR LEUKOCYTES - NO CHANGE WITH AGE

Aging has been associated with alterations in signal transduction for a number of neurotransmitter receptors in human tissues. Heterotrimeri c G proteins play a pivotal role in postreceptor information transduct ion, by coupling a variety of hormone and neurotransmitter receptors t o several intracellular effector functions. Developmental and age-rela ted changes in the abundance of specific G alpha subunits have been sh own in the human brain. In the present study, functional and quantitat ive measures of G proteins were conducted in human mononuclear leukocy tes obtained from 19 healthy subjects of increasing age. Gs protein fu nction, assessed through cholera toxin-sensitive beta-adrenergic and d opaminergic agonists induced increases in H-3-Gpp(NH)p binding capacit ies to membranes of mononuclear leukocytes, and Gi protein function, a ssessed through pertussis toxin-sensitive muscarinic agonist induced i ncrease in guanine nucleotide binding capacity, were found to be unalt ered by increasing age. Immunobloting analyses with specific polyclona l antibodies against G alpha(s), G alpha(i), and G alpha(q) subunit pr oteins in mononuclear leukocyte membranes obtained from the same subje cts showed that the quantities of these proteins in mononuclear leukoc ytes were as well independent of age. Insofar as age-related alteratio ns in cellular information transduction mechanisms in peripheral tissu es are important from the etiological, diagnostic, and pharmacological aspects of age-related disorders, it is important to know that both t he coupling of receptors to G proteins, the function of these proteins , and their abundance in human peripheral mononuclear leukocytes stays unaltered by the aging process.