Biomedical subjects

Q D Han

Publications and source records attributed to Q D Han.

At least 37 records · Page 2Linked to original sources

PubMed1997

[Sertindole, a novel alpha 1A-adrenoceptor selective antagonist].

The antagonism effect of sertindole on alpha 1-AR subtypes was studied by combining radiologand binding assays in three cloned alpha 1-AR subtypes stably expressed in human embryonic kidney 293 cells and contractile response experiment in isolated rat blood vessels. The results showed that the affinity for sertindole in the cloned alpha 1A-AR (pKI 8.90 +/- 0.17) was 69-fold (pKI 7.06 +/- 0.09) and 132-fold (pKI 6.78 +/- 0.07) higher than that for the cloned alpha 1B- and alpha 1D-AR, respectively. The pA2 values for sertindole in antagonizing NE-induced vasoconstriction in isolated rat aorta and renal artery were shown to fit well to the pKI values on cloned alpha 1D- and alpha 1A-AR, respectively. Pretreatment of membrane preparations with sertindole for 30 min significantly reduced the maximal binding capacities. (Bmax) of 125 IBE2254 to the three cloned alpha 1-AR subtypes without alteration of affinities (KD values). In the presence of sertindole, the Bmax of 125IBE2254 binding to the cloned alpha 1-ARs were not significantly changed, while the KD values were significantly increased. Thus, sertindole is a selective irreversible competitive alpha 1-AR antagonist with alpha 1A subtype.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1997

[Alteration of cardiac beta-adrenoceptors and subtypes with increasing age].

The alteration of cardiac beta-adrenoceptor (beta-AR) and subtypes in Wistar rats of 48 and 10 weeks old were investigated by radioligand binding assay and functional determination of isolated perfused left atria. The results indicated that: (1) The density of cardiac total beta-AR was downregulated about 28% in 48 weeks old rats as compared with rats of 10 weeks old for both beta 1- and beta 2-AR; (2) The sensitivity of beta-AR and subtypes to isoproterenol in isolated perfused atria was significantly lowered in rats of 48 weeks old; (3) The beta-AR mediated contractile effect of 10 weeks old rat hearts was mainly attributed to beta 1 type, but equally to both beta 1 and beta 2 types in 48 weeks old rat hearts; (4) The two receptor subtypes showed mutually potentiation effect in 10 weeks old rat hearts when stimulated simultaneously, but only additive in 48 weeks old rat hearts.

Aging↗

PubMed1997

[Different susceptibilities to desensitization of three alpha 1-adrenoceptor subtypes induced by sustained norepinephrine stimulation].

cDNAs for the bovine alpha 1A-, hamster alpha 1B- and rat alpha 1D-adrenoceptors (AR) were transfected into human embryonic kidney 293 (HEK293) cells by calcium phosphate precipitation and stably expressed at high levels. The inositol phosphates (InsPs) accumulation was measured by the method of 3H-inositol incorporation and column chromatography. Susceptibilities to the desensitization of alpha 1-AR subtypes-mediated InsPs accumulation were determined in HEK 293 cells stimulated sustainedly by norepinephrine (NE). The NE-induced InsPs accumulation showed progressive decrease by NE pretreatment with increasing time of preincubation and concentration of NE in the cells transfected with all the alpha 1-AR subtypes. However, susceptibilities to the desensitization were different among the three subtypes. The desensitization of alpha 1A-AR took place earliest and needed lowest concentration of NE. The desensitization of alpha 1D-AR appeared to be the latest and needed hightest concentration of NE, while alpha 1B-AR stood in between.

Adrenergic alpha-Agonists↗

PubMed1997

[Absence of point mutation in the third intracellular loop of alpha 1B- and alpha 1D adrenergic receptor in the aortae of spontaneously hypertensive rats].

Our previous experiments showed that the basal level of inositol phosphates (IPs) accumulation in the aorta was higher in spontaneously hypertensive rats (SHR) than in WKY rats. According to the constitutive activity hypothesis for G-protein coupling receptors, we inferred that point mutations might possibly exsit in the third intracellular loop of alpha 1B- and/or alpha 1D-adrenergic receptor (AR), the main subtypes of alpha 1-AR mediating phosphatidylinositol hydrolysis in SHR aortae. This inference, however, was not demonstrated by the results of our PCR-SSCP analyses, which indicated that the increased basal level of IPs accumulation in the isolated aortae from SHR does not result from constitutive activity of alpha 1B- and alpha 1D-AR induced by point mutations of the third intracellular loop of the genes.

Animals↗

PubMed1997

[Changes of CGRP levels in plasma and CGRP mRNA in dorsal root ganglia during endotoxicosis in the rat].

To investigate the changes of both CGRP release and synthesis during endotoxicosis, CGRP mRNA in thoracolumbar dorsal root ganglia (DRG) was determined by the semi-quantity RT-PCR and the CGRP levels in plasma were measured by RIA. The results showed that plasma CGRP, but not mRNA, began to increase 30 min after endotoxin (5 mg/kg, i.v.) administration. On the other hand, the CGRP levels in plasma and CGRP mRNA in DRG were significantly increased by 142% and 32% respectively at the 3 h of injection and by 216% and 85% respectively at the 8 h of injection. The data suggest that not only the release of CGRP from the peripheral organs, but also the transcription of CGRP mRNA and synthesis of CGRP in sensory neurons are increased during the development of endotoxicosis in the rat. Presumably the DRG is an important source of CGRP release in the response to endotoxicosis.

Animals↗

PubMed1997

[Comparison of functional alpha 1-adrenoceptor subtypes in aortae between 12 month- and 10 week-old rats].

The distribution of alpha 1-adrenoceptor and its subtypes in isolated aortae was compared between 12 month- and 10 week-old Wistar rats by determinating vasoconstrictor responses. In the 12 month-old rats, compared with the 10 week-old rats, (1) the maximal contraction induced by norepinephrine (NE) was reduced, without significant alteration of pD2 value; (2) the inhibitory effect of chlorethylclonidine (an irreversible antagonist for alpha 1B and alpha 1D subtype) on NE-induced contraction was weaker; (3) using NE as an agonist, the pA2 value for WB4101 (an alpha 1A- and alpha 1D-selective antagonist) was not changed, but the pA2 value for BMY7378 (an alpha 1D-selective antagonist) was decreased, while the pA2 value for sertindole (an alpha 1A-selective antagonist) was increased. Thus, differently from the 10 week-old rats in which only alpha 1D-adrenoceptors mediate NE-induced contraction in aortae, both alpha 1A- and alpha 1D-adrenoceptors (mainly alpha 1A) mediate the response in the 12 month-old rats.

Adrenergic alpha-Agonists↗

PubMed1996

[Endotoxin causes release of calcitonin gene-related peptide (CGRP) from the isolated mesenteric arterial bed in rat].

Our previous work has shown that CGRP is released into the circulation during endotoxin or hemorrhagic shock in animals and septic shock in patients. We have also identified the blood vessels as a major source of production of circulating CGRP in the endotoxic rat. In the present study we determined whether ETX could directly trigger release of CGRP from CGRP-containing perivascular nerves in isolated mesenteric arterial bed (MAB) of rat. The results showed that ETX caused time- and concentration (10-100 micrograms/ml) -dependent release of CGRP. ETX (50 micrograms/ml) is increased by 20 fold CGRP in perfusate 10-15 min after ETX. Characterization of CGRP in perfusates by reverse-phase HPLC showed one predominant peak which coeluted with synthetic rat CGRP. Pretreated MAB with capsaicin or ruthenium red inhibited ETX-induced release of CGRP by 90% and 65% respectively. ETX-induced CGRP release was decreased under Ca2+-free perfusion by 80%. The data suggest that ETX directly trigger the release of CGRP from capsaicin-sensitive sensory nerve innervating blood vessels. The release of CGRP is dependent on extra-cellular Ca2+ and Ca2+-induced Ca2+ release from the intracellular Ca2+ store which is sensitive to ruthenium red.

Animals↗

PubMed1996

[Effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its subtypes in rat].

The effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its subtypes and beta-adrenoceptor were observed by the method of radioligand binding assay in rat. The experiments showed: (1) .OH and O??? reduced the Bmax of alpha 1-adrenoceptors binding to 125IBE2254 by 55% and 36%, respectively. (2) The KI values of alpha 1-adrenoceptors were increased by .OH (by 171%), but not by O2-. (3) Both .OH and O2-. increased the ratio of alpha 1A vs alpha 1B subtypes. (4) beta-adrenoceptors were not changed by either .OH or O2-. (5) Oxygen free radical scavengers mannitol and superoxide dismutase were capable of preventing the changes of alpha 1-adrenoceptor and its subtypes induced by oxygen free radicals. The above results suggest that oxygen free radicals can reduce the number and affinity of myocardial alpha 1-adrenoceptors, of which the alpha 1B subtype is more accessible to the changes.

Animals↗

PubMed1996

[Alteration of cardiac alpha 1-adrenergic receptor subtypes in cardiac insufficient rat].

The cardiac insufficiency was produced by simultaneous constriction of abdominal aortae and renal artery in rat. Radioligand binding and reverse transcription-polymerase chain reaction (RT-PCR) were used respectively to determine the alterations of cardiac alpha 1-adrenergic receptor (alpha 1-AR) subtypes at protein level and gene transcription level. The Scatchard analysis of 125I-BE 2254 saturation curves showed that in cardiac insufficient rat hearts the KD values (229 +/- 32 vs 195 +/- 15 pmol/L) and the Bmax values (102 +/- 12 vs 96 +/- 17 fmol/mg) were not significantly different from those of control hearts. In the insufficient rat hearts, the inhibition of alpha 1-AR specific binding by WB 4101 showed that the high affinity sites (alpha 1A + alpha 1D) were increased from the 22 +/- 5% of the control to 51 +/- 7% (P < 0.01). The alpha 1A-AR mRNA level was increased, alpha 1B-AR mRNA level decreased while alpha 1D-AR unchanged. The results suggest that in cardiac insufficient rat hearts the subtype composition is altered as shown by increased alpha 1A-AR, decreased alpha 1B-AR and unchanged alpha 1D-AR, although the total amount of alpha 1-AR is unchanged.

Animals↗

PubMed1996

[Effects of inflammatory mediators on the release of CGRP from isolated mesenteric arterial bed of rat].

The purpose of the present study was to observe whether inflammatory mediators, such as: Prostaglandin E2 (PGE2), Bradykinin (BK), Histamine (HIS), Platelet active factor (PAF) and 5-hydroxytryptamine (5-HT), directly triggered the release of CGRP from perivascular nerves in isolated rat mesenteric arterial bed. The results showed that PGE2 (1-100 mumol/L) and BK (5-10 mumol/L) caused time- and concentration-dependent CGRP release, but HIS, PAF and 5-HT did not show significant effects. Our data indicate that PGE2 and BK are the major inflammatory mediators in triggering the release of CGRP from the perivascular CGRP-containing nerve.

Animals↗

PubMed1996

[A study on the change of myocardial neuropeptide Y release induced by electric stimulation and myocardial ischemia in guinea pig heart].

Electrical stimulation of the left stellate ganglion in guinea pig heart evoked a calcium-dependent, exocytotic release of neuropeptide Y (NPY). Stimulation after 10 min of global ischemia (S2), compared with control period stimulation (S1), had no significant effect on the NPY release. The release of NPY produced by the same stimulation after 20 min of ischemia was inhibited to certain extent (S2/S1: 0.72, P < 0.05), whereas the inhibition of NPY release disappeared after 5 min of reperfusion (with a S2/S1 of 1.01). Ischemia alone, without electric stimulation, did not apparently induce NPY release, suggesting that electrical stimulation may induce a calcium-dependent, exocytotic release of NPY. It is further suggested that the inhibition of NPY release may be produced by some metabolites and the abolishment of the inhibition after reperfusion may be due to washout of the metabolites.

Animals↗

PubMed1996

[The roles of nitric oxide and prostaglandins in the endotoxin-induced release of calcitonin gene-related peptide (CGRP) in rat mesenteric artery].

The mechanism of endotoxin (ETX) -induced release of CGRP was studied in isolated mesenteric arterial bed. ETX (50 micrograms/ml) caused a 16-fold increase of the release of CGRP. The effect of ETX was enhanced by L-arginine (L-Arg), a substratum of nitric oxide synthase (NOS), by 41%, but inhibited by NG-nitro-L-arginine (L-NNA), an selective inhibitor of NOS, L-NNA, and methylium blue (MB), an inhibitor of guanylate cyclase, respectively by 35% and 36%. These observations suggested that the effect of ETX is, at least partially, mediated by elevation of intracellular cGMP induced by NO. When endothelial cells were removed, the above responses of L-NNA and L-Arg still existed, indicating that ETX activated neuronal, rather than endothelial, NOS. Indomethacin and ibupofen, inhibitors of cyclooxygenase, also inhibited ETX-induced CGRP release by 34% and 39% respectively. When L-NNA and indomethacin were both incubated, no additive effects were discernible. The data suggest that ETX triggers CGRP release partially through activation of NOS located in perivascular sensory nerve and increase of NO, which is followed by activation of cyclooxygenase.

Animals↗

PubMed1996

[Mechanisms of the calcium influx across the plasma membrane].

The Ca2+ influx is mainly mediated by voltage-dependent Ca2+ channels and store depletion-dependent Ca2+ channels. The former, which mainly acts to regulate Ca2+ influx in excitable cells, is relatively clear; However, the later, which mainly functions in nonexcitable cells, remains enigmatically complicated. Following activation of the intracellular Ca2+ store, the depletion of the store provides a signal for activating Ca2+ entry across the plasma membrane via presently unknown mechanisms. This paper reviews the rapid progress in this field.

Animals↗

PubMed1996

[Antagonistic effect of tetrahydroproberberine homologues on alpha 1-adrenoceptor].

The antagonistic effect of tetrahydroproberberine (THP) homologues on alpha 1-adrenoceptor was studied by combination of radioligand binding assays and measurements of vasoconstriction responses. The results showed that l-tetrahydropalmatine (l-THP), l-stepholidine (l-SPD), THPB-18 and tetrahydroberberine (THB) competitively inhibited the 125I-BE2254 specific binding in rat cerebral cortex with pK1 values of 5.54 +/- 0.36, 5.56 +/- 0.47, 5.75 +/- 0.56 and 6.01 +/- 0.60, respectively, and the Hill efficiency was not significantly different from unity. They inhibited phenylephrine-induced constrictions with pA2 values of 5.48 +/- 0.58, 5.66 +/- 0.54, 5.64 +/- 0.34 and 5.45 +/- 0.76, respectively, and the slopes of Schild plot were not significantly different from unity. The results indicate that the 4 THP homologues are non-subtype selective competitive antagonists for alpha 1-adrenoceptor with similar affinities.

Adrenergic alpha-Antagonists↗

PubMed1995

[Effects of long-term atenolol treatment on beta-adrenoceptor subtypes in rat heart].

The effects of long-term beta 1-AR selective antagonist atenolol treatment on beta-adrenoceptor subtypes were studied by radioligand binding assay, function determination and cAMP accumulation measerment in rat heart. The reasults showed that during long-term administration of atenolol: (1) The density of total beta-AR was increased by approximately 57%; the positive inotropic response and cAMP formation induced by activation of beta-AR were also enhanced. (2) The 125I-pindol competitive inhibition curve for CGP20712A showed that there were no significant difference in the percentage of beta 1- and beta 2-AR sites between the atenolol treated rats and the control rats; pA2 values for selective beta 1-AR antagonist CGP20712A and pKB values for selective beta 1-AR antagonist ICI 118, 551 were not significantly different in the two groups. The results suggested that beta 1- and beta 2-adrenoceptors were upregulated not only in density but also in positive inotropic effect to the same extent.

Animals↗

PubMed1995

[A study on hypotensive mechanism of adrenomedullin (13-52)].

In the present study the hypotensive mechanism of AdM (13-52) was investigated in rats, both in vitro and in vivo. It was found that the hypotensive effect of AdM (13-52) could be partially inhibited by L-NG-nitro-arginine (LNNA), an inhibitor of nitric oxide synthase. The vasodilator effect of AdM (13-52) was dependent on vascular endothelium and inhibited by LNNA in a dose-dependent manner. This LNNA induced inhibitory effect could be reversed with L-Arginine. In addition, the vasodilator effect of AdM (13-52) disappeared with methylene blue (MB), which blocked cGMP formation. Using radioimmunoassay it was shown that LNNA lowered, but AdM (13-52) elevated the vascular cGMP content, while vascular cGMP content was not altered by co-application of AdM (13-52) and LNNA. The above results suggest that the vasodilator effect of AdM (13-52) might be mediated by nitric oxide.

Adrenomedullin↗

PubMed1995

Increase of release of neuropeptide Y in vitro from platelets of spontaneously hypertensive rats.

AIM: To investigate the pathophysiological role of platelet neuropeptide Y (NPY) in hypertension. METHODS: The content of NPY in plasma and platelets from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKR) were measured by radioimmunoassay. RESULTS: There was no difference in NPY concentration between SHR plasma and WKR plasma (2.1 +/- 1.0 vs 1.8 + 1.0 microgram.L-1), but higher amounts of NPY in SHR platelets than in WKR platelets (32 +/- 6 vs 22 +/- 9 micrograms.L-1, P < 0.05). The platelet aggregation and the release of NPY from platelets induced by thrombin and collagen were increased in SHR; ADP did not cause NPY release from platelets, although it produced severe aggregation in both SHR and WKR. CONCLUSION: The content of NPY in platelets and thrombin- and collagen-induced NPY release from platelets are higher in SHR than in WKR.

Animals↗

PubMed1995

[Progress in adrenoceptor research].

According to pharmacological characteristics and molecular cloning, adrenoceptor is divided into 3 types, and each type contains at least 3 subtypes. The molecular structure of adrenoceptor fits common model of G protein coupled receptors on membrane surface. The structure-function relationship has been basically elucidated by mutation techniques. The ligand binding characteristics are decided by the structures in transmembrane domains, while the G protein coupling sites are in the third intracellular loop. There are extensive crosstalks among the subtypes of adrenoceptor. According to the mechanisms, the crosstalks can be divided into 4 types.

Animals↗