ANTIPROLIFERATIVE EFFECTS OF A02011-1, AN ADENYLYL-CYCLASE ACTIVATOR, IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS OF RAT

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Title:	ANTIPROLIFERATIVE EFFECTS OF A02011-1, AN ADENYLYL-CYCLASE ACTIVATOR, IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS OF RAT
Authors:	YU, SM;CHENG, ZJ;KUO, SC
Contributors:	藥學院藥化所;CHINA MED COLL,INST PHARMACEUT CHEM,TAICHUNG,TAIWAN
Date:	1995
Issue Date:	2010-09-24 15:06:07 (UTC+8)
Publisher:	STOCKTON PRESS
Abstract:	Previous studies have shown that pregnancy is associated with a decrease in cholinergic function in the rabbit urinary bladder. The present study aimed at evaluating the effects of pregnancy on the autonomic function of the rat urinary bladder and to elucidate whether progesterone is responsible for such alterations. Female Wistar rats, 3 months old, were divided into four groups: (1) 2-week pregnant rats; (2) rats given daily intramuscular injection of progesterone 5 mg/kg for 2 weeks; (3) rats given intramuscular injections of vehicle for 2 weeks, and (4) controls. Cystometry showed a significant increase in bladder capacity in the pregnant rats. The wet weight of the pregnant rat bladder was also significantly increased. Histologic study revealed increased bladder wall thickness with interstitial edema and urothelium proliferative changes to a papillary configuration in these pregnant bladders. Bladder muscle strip study showed significantly reduced maximum contractile responses to acetylcholine and methoxamine in the pregnant and the progesterone groups. Muscarinic receptor binding study demonstrated reduced B-max in the pregnant rats and rats receiving progesterone injections (control group B-max = 57 +/- 11, pregnant group B-max = 44 +/- 8, p < 0.05; progesterone group B-max = 40 +/- 7, vehicle group B-max = 58 +/- 9 fmol/mg protein, p < 0.05). The contractile response to lower concentrations (10(-6) mol/l to 10(-4) mol/l) of ATP was elevated in the pregnant rats. It is concluded that: (1)suppressed bladder contractility during pregnancy is due to reduction in cholinergic and less importantly in alpha-adrenergic function of the organ, (2) the reduced cholinergic responsiveness is caused by decreased muscarinic receptor density; (3) the bladder affinity for ATP is increased during pregnancy, and (4) exogenous progesterone administration mimicks some but not all of the pregnancy effect.
Relation:	BRITISH JOURNAL OF PHARMACOLOGY 114(6):1227-1235
Appears in Collections:	[Graduate Institute of Pharmaceutical Chemistry] Journal articles

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