Changes in muscarinic responsiveness, muscarinic receptor density and Ca2+ mobilization of the urinary bladder in streptozotocin-induced diabetic rats.
Functional changes in the urinary bladder obtained from diabetic rats were investigated by determining the responsiveness to acetylcholine (ACh). Maximal contraction of the detrusor strips in response to ACh was significantly enhanced in the diabetic rats. Ca(2+)-induced contracture of the detrusor strips, which had been incubated with 10(-3) M ACh in the presence of nicardipine in Ca(2+)-free medium, was significantly augmented in diabetic rats. Ca(2+)-contracture in Ca(2+)-free, isotonic high-K+ (60 mM) medium was not changed in diabetic state. The density of muscarinic receptors to 3H-QNB was significantly higher in the bladder from diabetic rats compared to age-matched control rats. These results suggest that tone of the autonomic nervous system in the bladder may be decreased in diabetes and, thus, compensatory increase in density of muscarinic receptors may occur. Furthermore, an increased contractile response of the detrusor strips of the urinary bladder to ACh in diabetic rats also may be due to an increased influx of extracellular Ca2+ through the receptor-operated Ca2+ channels but not the voltage-dependent Ca2+ channels.
Kamata
K
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Inoue
K
K
Kasuya
Y
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D001786:Blood Glucose; D015220:Calcium Channels; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D009529:Nicardipine; D000109:Acetylcholine; D002118:Calcium