Differential regulation of bladder beta-adrenergic and muscarinic cholinergic receptors in experimental diabetes.
To determine the contribution of diuresis-induced bladder hypertrophy, which accompanies the diabetic state, on the biochemical and functional alterations observed in the diabetic bladder, we compared three experimental groups: 8-wk streptozocin (STZ)-induced diabetic rats, 8-wk sucrose-fed diuretic rats, and age-matched controls. Diabetic and sucrose-fed rats had higher water intake, higher urine output, and larger bladders than controls. Diabetic rats had lower serum insulin levels, lower body weights, and higher serum glucose levels than either control or sucrose-fed animals. Receptor binding studies with [3H]quinuclidinyl benzilate in bladder dome demonstrated an upregulation of muscarinic receptors in diabetic and sucrose-fed rats compared with controls. Parallel binding studies with [3H]dihydroalprenolol and [125I]iodopindolol showed an upregulation of beta-adrenergic receptors in diabetic but not in sucrose-fed bladder domes. Carbachol induced larger contractile responses in diabetic and sucrose-fed than in control bladder dome muscle strips. isoproterenol relaxed KCl-contracted detrusor strips from both diabetic and sucrose-fed rats to a greater degree and with a higher affinity than detrusor strips from controls. Our data show that overdistension and increased workload per se contributed to the upregulation of muscarinic but not to the upregulation of beta-adrenergic receptors in STZ-induced diabetes. Furthermore, the magnitude of carbachol-induced contractions correlated with muscarinic receptor upregulation, whereas the magnitude of isoproterenol-induced relaxation did not correlate with changes in the density of the beta-adrenergic receptors. Thus, it appears that different regulatory mechanisms are involved in diabetes-induced alterations in muscarinic and beta-adrenergic receptors in bladder dome.
Latifpour
J
J
Section of Urology, Yale University School of Medicine, New Haven, Connecticut 06510.
Nishimoto
T
T
Marian
M J
MJ
Yoshida
M
M
Weiss
R M
RM
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004231:Diuresis; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010869:Pindolol / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013395:Sucrose / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D013395:Sucrose; D004082:Dihydroalprenolol; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D010869:Pindolol; D007545:Isoproterenol