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51.
Viktoria Werkstrm Katarina Persson Karl-Erik Andersson 《British journal of pharmacology》1997,121(8):1605-1612
- To investigate further the release, localization and identity of a non-nitrergic mediator of smooth muscle relaxation in the female pig urethra, we studied the effects of drugs acting at α2-adrenoceptors or K+ channels, the effects of capsaicin and chemical sympathectomy, and the actions of several transmitter candidates.
- Electrical field stimulation (EFS; frequencies above 12 Hz) of spontaneously contracted smooth muscle strips from the female pig urethra evoked long-lasting, frequency-dependent relaxations in the presence of prazosin, scopolamine, and NG-nitro-L-arginine. Treatment with the selective α2-adrenoceptor agonist UK-14 304 markedly reduced the relaxations evoked by EFS at all frequencies tested (16–30 Hz). The inhibitory effect of UK-14 304 was completely antagonized by the α2-adrenoceptor antagonist rauwolscine. The muscarinic M1 receptor antagonist, pirenzepine, or exogenously administered carbachol, did not have any effects on the electrically evoked relaxations.
- Inhibition of high conductance Ca2+ activated K+ channels by iberiotoxin or charybdotoxin significantly enhanced the relaxations evoked by EFS at all frequencies. However, inhibition of voltage-sensitive K+ channels with 4-aminopyridine or dendrotoxin-1, treatment with the ATP-sensitive K+ channel blocker, glibenclamide, or treatment with the high and low conductance Ca2+ activated K+ channel blockers, tetraethylammonium chloride and apamin, had no effect on the relaxations evoked by EFS.
- Electrically evoked relaxations were not affected by adrenergic denervation with 6-hydroxydopamine (6-OHDA) at any frequency. However, treatment with 6-OHDA abolished prazosin-sensitive electrically induced contractions, and a long-lasting relaxation was revealed. Treatment with capsaicin, believed to damage selectively a subpopulation of primary afferent fibres, did not affect basal tone or relaxations evoked by EFS.
- Exogenously applied vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38, adenosine, ATP and 5-hydroxy-tryptamine caused relaxations of the urethral preparations, whereas prostaglandin E2 and calcitonin gene-related peptide had no effects. VIP 10-28, α, β-methylene-ATP, reactive blue-2, suramin or indomethacin did not reduce the electrically-evoked relaxations at any frequency. However, the relaxations were slightly reduced by trypsin or α-chymotrypsin.
- The present results suggest that the release of the unknown mediator in the female pig urethra can be modulated via α2-adrenoceptors and high conductance Ca2+ activated K+ channels. Furthermore, the mediator does not appear to be localized to or released from adrenergic or capsaicin-sensitive sensory nerve-endings. The identity of the transmitter remains to be established.
52.
Makoto Iwata 《Surgery today》1994,24(12):1056-1067
The pathophysiological conditions following 84% hepatectomy were examined in terms of the changes in thromboxane A2 (TxA2) and prostaglandin I2 (PGI2) in canine model. OKY-046, TxA2 inhibitor, and OP-2507, a PGI2 analog, were administered to evaluate the possibility of extending hepatic resection. The 2-week survival rate following 84% hepatectomy significantly improved after the administration of OKY-046 and OP-2507, from 12.5% to 58.3% and 75.0%, respectively. Furthermore, OP-2507 significantly improved impaired hepatocyte and sinusoidal endothelial cell function after 84% hepatectomy, resulting in a satisfactory recovery to the preoperative levels. Within 24 h after 84% hepatectomy, the plasma levels of thromboxane B2 (TxB2) increased significantly, and the 6-keto-prostaglandin Fl (6-KF) levels became slightly elevated. OKY-046 and OP-2507 decreased TxB2 and increased 6-KF in the plasma, resulting in the maintenance of sufficient blood flow in the portal vein and hepatic tissue and the mitigation of microcirculatory disorders. Moreover, the cytoprotective effects of the two drugs inhibited functional impairment of the residual liver. In conclusion, abnormal prostaglandin metabolites were produced after 84% hepatectomy, being involved in residual liver disorders. However, the administration of either an inhibitor of TxA2 synthesis or PGI2 analog ameliorated the functional impairment of the residual liver, which suggests their potential value for extending the resectability of the liver from what is presently feasible.An abstract of this study was presented at the 92nd Annual Meeting of the Japan Surgical Society held in 1992. 相似文献
53.
Several approaches to the separation of four stereoisomers, 1–4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5–8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1–4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-l-(l-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5-dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1–4 or 5–8. The details of chiral separations using various methods and separation () and capacity factors (k) of the derivatized isomers 1–8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S
1
S
2 (5), and the heat (HD) and light (LD) degradation products of 1 as R
1
S
2 (3) and S1
S
2 (5), respectively. 相似文献
54.
A new type of ultra-short acting -blocker which might prove advantageous in treating acute arrhythmias was designed, synthesized and investigated. Based on the soft drug inactive metabolite approach, the inactive phenylacetic acid metabolite of both metoprolol and atenolol was reactivated by esterification with sulfur-containing aliphatic alcohols. Since the sulfur-containing moieties are labile to the ubiquitous esterases, the new compounds should be inactivated by a one step enzymatic cleavage back to the inactive phenylacetic acid derivative. Pharmacological and pharmacokinetic profiles of the new compounds were evaluated in rats and rabbits. Isoproterenol-induced tachycardia was inhibited with short-term infusion of each compound. This tachycardia blocking effect rapidly disappeared upon termination of infusion, while -blocking activity was 2–4-fold longer after comparable doses of the short-acting -blocker, esmolol. The rapid recovery from the -receptor blockade is believed due to fast hydrolysis of the soft drugs in the body. This is supported from in vitro results showing the tl/2 of esmolol is about 10-fold longer than the new soft drugs in rat, rabbit, dog and human blood. Hydrolysis studies in phosphate buffered solutions indicated that the esters are labile to base-catalyzed hydrolysis. However, the relative t1/2 values measured in biological media compared to phosphate buffered solution clearly support rapid enzymatic cleavage of the soft drugs. Interestingly, one of the soft -blockers, the sulfonyl ester derivative, showed a unique property of exhibiting good -receptor blocking activity without significant hypotensive action. 相似文献
55.
通过动态力学参数温度谱,研究了尼龙1010/6、尼龙1010/66两个共聚物系列的动态力学参数与组成的关系。研究表明尼龙1010/6、尼龙1010/66在测试温度范围内出现三个明显的松驰转变:α、β、γ,其中各共聚物的β、γ松驰温度相差不大,而α松驰温度随组成改变有明显改变。一般均聚物的α松驰温度较高,共聚物的α松驰温度均低于均聚物,二个系列以尼龙1010/6(29.8/70.2)、尼龙1010/ 相似文献
56.
Brenda Costall Robert J. Naylor Connie C. W. Tan 《Naunyn-Schmiedeberg's archives of pharmacology》1983,323(2):155-161
Summary Field stimulation of circular smooth muscle of guinea-pig stomach from the regions of the cardia and fundus caused contraction responses at low stimulation frequencies (0.25–1 Hz) with relaxation at higher frequencies (1–10 Hz), whilst tissues of the body and antrum responded with contraction throughout the frequency range. Atropine (10–9–10–8 M) antagonised the contraction responses of all tissues, with relaxation developing at higher concentrations (except for antral tissue). In contrast, metoclopramide (10–8–10–6 M) caused modest (cardia, fundus) or marked (body, antrum) enhancement of contractions to field stimulation, whilst domperidone (10–8–10–7 M), haloperidol (10–8–10–6 M), prazosin, propranolol and methysergide (10–8–10–6 M) failed to modify the contraction responses. However, whilst yohimbine and guanethidine failed to modify the contractions of the cardia, fundus and body tissues, those of the antral preparations were antagonised by nanomolar concentrations of yohimbine and by guanethidine (10–6–5×10–5 M). To optimise the relaxation responses for study, atropine was included in the physiological solution. Relaxation to field stimulation of preparations from the body and cardia, but not the fundus, was antagonised by reserpine pretreatment (5 mg/kg i.p., 24h), addition of guanethidine (10–5–10–4 M), phentolamine, prazosin or propranolol (10–7–10–6 M) (the effects of prazosin and propranolol being additive). Higher concentrations of haloperidol and domperidone antagonised the relaxation responses of the body preparations only. Metoclopramide, yohimbine and methysergide (10–8–10–6 M) were ineffective. Thus, it is concluded that the contractile effects of the 4 stomach areas to field stimulation reflects a major cholinergic involvement, with an additional 2-adrenoceptor contractile component in antral tissue. Relaxation responses of cardia and body tissue involve 2- and -adrenoceptors plus a further, unidentified, non-adrenergic component; the latter represents the total relaxation response of the fundic preparation. 相似文献
57.
Rudolf Kadatz Walter Kobinger Alexander Walland 《Naunyn-Schmiedeberg's archives of pharmacology》1976,292(2):97-103
Summary 2,2-[(4,8-bis(diethylamino)-pyrimido [5,4-d]-pyrimidine-2,6-diyl)di-(2-methoxyethyl)imino]diethanol), RA 642, combines hypertensive and vasodilating effects. In anaesthetized animals arterial blood pressure was increased by i.v. doses of 0.25–4 mg/kg in cats and 0.025–0.25 mg/kg in dogs. In conscious dogs, 25 mm increase of mean blood pressure was achieved with 0.2 mg/kg i.v. and 18.8 mg/kg p.o. Cerebral blood flow was enhanced and calculated cerebral vascular resistance was reduced by RA 642. Total peripheral resistance was diminished by 0.25–1.0 mg/kg i.v. A vasodilatation of femoral and coronary vessels was shown after intraarterial injection. This effect as well as a BaCl2-antagonism in the isolation ileum is explained by a papaverine-like relaxant effect on smooth muscle. Activity on peripheral adrenergic receptors was excluded. Hypertension was abolished in spinalized cats, indicating a central mechanism of this effect. 相似文献
58.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(1):25-30
Enterolactone and enterodiol are the main mammalian metabolites of dietary butyrolactone type lignans. The study of biological properties and potential health effects of these compounds requires isotopically labelled compounds as standards for quantitative measurements. An expedient deutero‐labelling method for enterolactone is to use the D3PO4·BF3/D2O complex at room temperature which will exchange all eight aromatic hydrogens, even from inactivated meta positions, to form [2,4,5,6,2′,4′,5′,6′‐2H8]‐enterolactone in 74% yield and 99% isotopic purity. [2,4,5,6,9,9,2′,4′,5′,6′‐2H10]‐Enterodiol was prepared from [2,4,5,6,2′,4′,5′,6′‐2H8]‐enterolactone by reduction with LiAlD4 which introduces two more deuterium atoms into the molecule. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
59.
60.
The safety, predictability, and ease of intravenous administration of nitroglycerin (NTG) have been firmly documented. In
recent years, intravenous NTG has come to the attention of the obstetrician as a potent uterine relaxant. Intravenous nitroglycerin
has been used to relax the uterus during manual extraction of retained placenta and to permit replacement of a contracted,
completely prolapsed, inverted uterus. The use of this agent as a tocolytic has previously been reported in cesarean delivery
of twins, in cases of intra partum external cephalic version, and for internal intrapartum podalic version of the second twin.
This new procedure was also used for fetal head entrapment after vaginal breech delivery. The authors report a review of the
literature about this subject.
Received: February 1997 / Accepted: 20 June 1997 相似文献