Alterations in G-proteins and beta-adrenergic responsive adenylyl cyclase in rat urinary bladder during aging.
Decreased response of bladder to beta-adrenergic stimulation with aging is related to decreased adenylyl cyclase activity and possibly to changes in guanine nucleotide regulatory protein (G-protein) content or function. G-protein content was quantified by Western blot analysis using antibodies to Gsalpha, Goalpha, and Gialpha in 21-day-old (weanling), 90-day-old (young adult), 6-month-old (adult), and 24-month-old (old) rat bladders. Gi/Go function in bladders with aging was measured by ADP-ribosylation with pertussis toxin. Content of Gsalpha, Goalpha, and Gialpha was lower in 90-day-old bladder than in 21-day-old bladder. Gsalpha content was similar in the 21-day-, 6-month-, and 24-month-old bladders. Gialpha content as well as pertussis toxin-catalyzed ADP-ribosylation was higher in 24-month-old bladders than in 21- and 90-day-old bladders. Pertussis toxin-catalyzed ADP-ribosylation of bladder membranes and treatment of bladder with protein kinase A inhibitors reversed the age-dependent decline in isoproterenol stimulation of adenylyl cyclase. Decreases in beta-adrenergic-induced relaxation response with age in rat bladder are due in part to increases in the content and functional activity of pertussis toxin-sensitive G-protein.
Derweesh
I H
IH
Section of Urology, Yale University School of Medicine, New Haven, CT 06520-8041, USA.
Wheeler
M A
MA
Weiss
R M
RM
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002227:Carbazoles; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000201:enzymology / Q000378:metabolism; D037342:Pertussis Toxin; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000201:enzymology / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000318:Adrenergic beta-Agonists; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; C057416:KT 5720; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol