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. Heterotrimeric G proteins play a pivotal role in postreceptor information transduction, by coupling a variety of hormone and neurotransmitter receptors to several intracellular effector functions. Developmental and age-related changes in the abundance of specific G alpha subunits have been shown in the human brain. In the present study, functional and quantitative measures of G proteins were conducted in human mononuclear leukocytes obtained from 19 healthy subjects of increasing age. Gs protein function, assessed through cholera toxin-sensitive beta-adrenergic and dopaminergic agonists induced increases in 3H-Gpp(NH)p binding capacities to membranes of mononuclear leukocytes, and Gi protein function, assessed through pertussis toxin-sensitive muscarinic agonist induced increase in guanine nucleotide binding capacity, were found to be unaltered by increasing age. Immunobloting analyses with specific polyclonal antibodies against G alpha s, G alpha i, and G alpha q subunit proteins in mononuclear leukocyte membranes obtained from the same subjects showed that the quantities of these proteins in mononuclear leukocytes were as well independent of age. Insofar as age-related alterations in cellular information transduction mechanisms in peripheral tissues are important from the etiological, diagnostic, and pharmacological aspects of age-related disorders, it is important to know that both the 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.
Barki-Harrington
L
L
Department of Clinical Pharmacology, Faculty for Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Nechamkin
Y
Y
Schreiber
G
G
Avissar
S
S
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood*; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood* / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008875:Middle Aged
D006165:Guanylyl Imidodiphosphate; D019204:GTP-Binding Proteins