摘要:

We studied the effects of 37 flavonoids on prostaglandin endoperoxide synthase (EC 1.14.99.1) purified from sheep vesicular glands. Nonplanar flavans were more potent inhibitors than planar flavones and flavonols (IC50 values were, e.g., 40 µmol/l for catechin and epicatechin, 110 µmol/l for galangin, 490 µmol/l for quercetin and 450 µmol/l for kaempherol). Different inhibition mechanisms were observed, i.e. uncompetitive inhibition for nonplanar flavonoids and competitive or noncompetitive inhibition for planar flavonoids. Potent inhibitors in the group of flavones were substances with an o-dihydroxy structure in the B ring and in the group of flavonol substances with two hydroxyl groups in position 5 and 7 of the A ring. None of the flavanones studied caused significant inhibition, except for the fiavanone-3-ol, silibinin (silybin), which caused potent inhibition with an IC50 of 120 µmol/l. Several flavonoids, which were able to inhibit the prostaglandin endoperoxide synthase at higher concentrations, were also able to stimulate the enzyme at lower concentrations. These results indicate that the flavonoids should be divided into two groups according to their capacity to inhibit the prostaglandin endoperoxide synthase, represented by planar and nonplanar substances as in each group a close correlation between structure and inhibitory activity was obse

ISSN:0031-7012    

DOI:10.1159/000138867

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138943

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138944

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138946

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

β-Adrenoceptors have been demonstrated in the urinary bladders of many animals including the guinea pig. However, there is little information on the subtypes involved in the antispasmodic activity of β-adrenoceptor activation in the guinea-pig detrusor. The present study uses the non-selective β-agonist isoproterenol, the antagonist nadolol, the β2-selective agonists salbutamol and terbutaline, the antagonist ICI 118551, and the β1-selective antagonist metoprolol, to demonstrate functionally the subtypes existing in the guinea-pig detrusor. Isoproterenol dose-dependently reduces the myogenic activity in the guinea-pig detrusor induced by mild depolarization with 20 mM potassium in the tissue bath. At the supramaximal concentration of 30 µM, isoproterenol achieves 73 ± 2% of the reference maximal response. This activity of isoproterenol is reduced to 9 ± 5, 24 ± 6 and 54 ± 1 % in the total blockade of β, β1 and β2 with nadolol, metoprolol and ICI 118551, respectively. Consistently, salbutamol and terbutaline at the same concentration produce only 35 ± 1 and 38 ± 4% of the response, respectively. Thus, both β1- and β2-adrenoceptors are present in the detrusor of the guinea-pig urinary bladder. Although activation of either subtype results in antispasmodic action, the larger portion of the antispasmodic activity appears to be associated with the activation of the β

ISSN:0031-7012    

DOI:10.1159/000138868

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138947

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The potassium-induced release of 3H-norepinephrine (3H-NE) was examined in the rat caudal artery. A simple and reliable method was developed to examine stimulated neurotransmitter release from this highly innervated resistance vessel. The potassium-induced release of 3H-NE was dose- and calcium-dependent. Stimulated 3H-NE release was elevated in the spontaneously hypertensive (SHR) compared to age-matched Wistar-Kyoto (WKY) animals (p < 0.05). However, in animals at 5–6 weeks of age, where the blood pressure was not different between the SHR and WKY, the stimulation-induced release of 3H-NE was also not significantly different. Low salt diets for 7 days significantly decreased the potassium-induced release of 3H-NE from both 10- to 11-week-old SHR and WKY animals. High salt diets did not significantly effect 3H-NE release, even though the high salt diets for 7 days significantly increased the blood pressure in the SHR. The results suggest that the caudal artery is a good model to study stimulation-induced transmitter release and that elevated 3H-NE release plays a role in the development of hypertension in the SHR. Low salt diets, which did not lower blood pressure, were shown to decrease 3H-NE release. High salt diets elevated the blood pressure in the SHR but had no significant effect on stimulated 3H-NE releas

ISSN:0031-7012    

DOI:10.1159/000138869

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138948

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138949

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The ability of α2adrenoceptor agonists to inhibit vasopressin (VP)-stimulated cAMP accumulation in collecting tubules and to inhibit the antidiuretic effect of VP in rats is clearly established. However, in other species, such as the dog, α2-adrenoceptor-induced inhibition of VP action has not been convincingly demonstrated. In the present study, we examined the effects of epinephrine and other α2adrenoceptor agonists on VP-stimulated cAMP accumulation in inner medullary collecting tubule cells and/or cortical collecting tubules from a number of species. Epinephrine, oxymetazoline, clonidine, and guanabenz inhibited VP-induced cAMP formation in rat inner medullary collecting tubule cells with IC50ss ranging from 10 to 30 nM. However, epinephrine or guanabenz had no effect on VP-stimulated cAMP formation in cells from dog, pig, rhesus monkey, or human inner medulla. Similarly, epinephrine inhibited VP-induced cAMP accumulation in cortical collecting tubules dissected from rat kidneys but not from dog or rabbit kidneys. We conclude that there is a marked species difference in the ability of α2adrenoceptor agonists to inhibit VP-induced cAMP formation at the tubular level. This may explain the difficulty in demonstrating an α2adrenocep-tor agonist-induced inhibition of VP action in other species such as dog and

ISSN:0031-7012    

DOI:10.1159/000138870

出版商:S. Karger AG    

年代:1992

数据来源: Karger