ABSTRACT
Objective To investigate the effect of I1imidazoline receptor(I1R)on the expression and function of α2Aadrener-gic receptor(α2AAR)at the cellular level.Methods After sequencing and enzymatic identification,the mouse I1R and α2AAR plas-mids were transfected into CHO cells,respectively.The radioligand receptor binding assay and flow cytometry were used to select sin-gle cell clones,and the CHO cell lines stably expressing the mouse I1R or α2AAR were established.The CHO cell line that stably ex-presses both the mouse I1R and α2AAR were also established by the same technology and strategy.Then,the radioligand receptor bind-ing assay was used to determine the affinity and expression of α2AAR. Further,the effects of I1R on the α2AAR expression and the α2AAR agonist dexmedetomidine(DEX)-induced extracellular regulated protein kinase(ERK)phosphorylation were evaluated by the Western blotting.Results After transfection of mouse I1R and α2AAR plasmids,CHO cells grew normally.In the saturation binding experiments of membrane proteins from the CHO cells that stably expressed α2AAR,the Kdand Bmaxvalues of 3H-RX821002 were(0.96 ± 0.24)nmol/L and(0.29 ± 0.03)nmol/g protein,respectively.The expression levels of I1R were significantly increased in both the CHO cells expressing I1R and the CHO cells co-expressing α2AAR and I1R(P<0.05,P<0.01),when the cells that express exogenous I1R or α2AAR alone were trasfected again with the I1R plasmids.Moreover,in the CHO cells that transfected both I1R and α2AAR sta-bly,the I1R expression upregulated the α2AAR expression(P<0.01),and further increased the ERK phosphorylation induced by DEX through activating α2AAR(P<0.01).Conclusion I1R could upregulate the α2AAR expression and the ERK phosphorylation in-duced by DEX through activating α2AAR in the CHO cells that express exogenous I1R and α2AAR.This study presents a groundwork for further exploration of the relationship between I1R and α2AAR at the molecular level in future.
ABSTRACT
Objective To investigate the effect of agmatine or agmatine combined with yohimbine on morphine-induced psychological dependence in mice. Methods 1. Testing the effect of agmatine or agmatin combined with yohimbine on basal locomotor activity in 60 minutes. C57BL/6J male mice were divided into four groups:control group, agmatine (1,10,20,40 and 80 mg/kg) groups, yohimbine(0.3,1,2 and 8 mg/kg) groups and yohimbine(2 mg/kg)+ agmatine(80 mg/kg) group. 2. Testing the effects of drug pretreatment on morphine-induced hyperlocomotion in 60 minutes. Mice were divided into five groups: control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg)+ morphine(10 mg/kg) group,yohimbine(2 mg/kg)+ morphine(10 mg/kg) group and yohimbine(2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. 3. Observing the effects of agmatine or agmatine combined with yohimbine on morphine induced behavioral sensitization. The mice were administrated with morphine(10 mg/kg) on the 1st , 4th and 7th day and the locomotor activity of mice was recorded for 60 minutes. Mice were divided into four groups: control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg) + morphine(10 mg/kg) groups and yohimbine (2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. Results Our present study showed that agmatine(1-80 mg/kg) or yohimbine (0.3-2 mg/kg), a selective antagonist of α2-adrenoceptor, had no significant effect on basal locomotor and acute morphine-induced hyperlocomotion compared with those of control group. However, the distance in the group of agmatine combined with yohimbine followed by morphine for 60 min was(22 581.6±11 694.0) cm,which was significantly lower than the acute morphine group(37 577.9±9 657.4)cm(P<0.05). In the mophine-induced behavioral sensitization model, agmatine(1,20 and 80 mg/kg) alone had no effect on morphine-induced development of behavioral sensitization in mice. But, the combination of the two drugs significantly attenuated morphine-induced behavioral sensitization. The locomotor activities in the combination treatment groups were (21 112.7±5 586.7)cm,(37 672.7±10 518.8)cm and(47 681.0±15 845.3)cm, which were lower than those of morphine group (31 156.4±8 010.5) cm(P<0.01),(51 724.9±11 364.51)cm(P<0.05) and(63 572.2±12 151.2) cm(P<0.05) on the 1st , 4th and 7th day of experiment, respectively. Conclusion Our current results demonstrated that agmatine combined with yohimbine could decrease morphine-induced psychological dependence in mice. It may provide a new strategy for psychological dependence of morphine.
ABSTRACT
Objective To investigate the effect of agmatine or agmatine combined with yohimbine on morphine-induced psychological dependence in mice. Methods 1. Testing the effect of agmatine or agmatin combined with yohimbine on basal locomotor activity in 60 minutes. C57BL/6J male mice were divided into four groups: control group, agmatine (1,10,20,40 and 80 mg/kg) groups, yohimbine (0.3,1,2 and 8 mg/kg) groups and yohimbine (2 mg/kg) + agmatine (80 mg/kg) group. 2. Testing theeffects of drug pretreatment on morphine-induced hyperlocomotion in 60 minutes. Mice were divided into five groups: control group, morphine (10 mg/kg) group, agmatine (1,20 and 80 mg/kg) + morphine (10 mg/kg) group,yohimbine (2 mg/kg) + morphine (10 mg/kg) group and yohimbine (2 mg/kg) + agmatine (80 mg/kg) + morphine (10 mg/kg) group. 3. Observing the effects of agmatine or agmatine combined with yohimbine on morphine induced behavioral sensitization. The mice were administrated with morphine (10 mg/kg) on the 1st , 4th and 7th day and the locomotor activity of mice was recorded for 60 minutes. Mice were divided into four groups: control group, morphine (10 mg/kg) group, agmatine (1,20 and 80 mg/kg) + morphine (10 mg/kg) groups and yohimbine (2 mg/kg) + agmatine (80 mg/kg) + morphine (10 mg/kg) group. Results Our present study showed that agmatine (1-80 mg/kg) or yohimbine (0.3-2 mg/kg), a selective antagonist of a2-adrenoceptor, had no significant effect on basal locomotor and acute morphine-induced hyperlocomotion compared with those of control group. However, the distance in the group of agmatine combined with yohimbine followed by morphine for 60 min was (22 581.6&11 694.0) cm, which was significantly lower than the acute morphine group(37 577.9±9 657.4) cm(#<0.05). In the mophine-induced behavioral sensitization model, agmatine (1,20 and 80 mg/kg) alone had no effect on morphine-induced development of behavioral sensitization in mice. But, the combination of the two drugs significantly attenuated morphine-induced behavioral sensitization. The locomotor activities in the combination treatment groups were (21 112.7±5 586.7) cm, (37 672.7±10 518.8) cm and 47 681.0±15 845.3 cm, which were lower than those of morphine group (31 156.4&8 010.5) cm(#<0.01), (51 724.9&11 364.51) cm (P<0.05) and (63 572.2&12 151.2) cm (P<0.05) on the 1st , 4th and 7th day of experiment, respectively. Conclusion Our current results demonstrated that agmatine combined with yohimbine could decrease morphine-induced psychological dependence in mice. It may provide a new strategy for psychological dependence of morphine.
ABSTRACT
Nischarin is a novel protein interacting with integrin ?5 subunit.A series of studies have indicated that Nischarin plays an important role in inhibiting tumor cells migration and invasion.Meanwhile it may also serve as the functional I1-imidazoline receptor.To study this protein will be in favour of understanding the biological mechanisms of inhibiting cell migration and developing novel drugs such as inhibitors for tumor invasion.The article mainly reviews the recent progress in studies on Nischarin.
ABSTRACT
Objective To investigate the effects of clonidine on the expression of myocardial ? subunit of inhibitory G protein (Gi?) in severely scalded rats and the mechanisms. Methods A scald model of 30% total body surface area Ⅲdegree burn on the back of rats was established. The basal and Gpp (NH) p, forsklin stimulated activity of adenylate cyclase (AC), and Gi? in cardiac myocytes were determined by indirect enzyme radiochemical assay and Western blotting, respectively. Results Clonidine at the dosage of 1-3 mg?kg -1 inhibited significantly the increase in the myocardial Gi? levels. Clonidine at the dosage of 0.3-3 mg?kg -1 partially reversed the decrease in the basal activity, and clonidine at the dosage of 1-3 mg?kg -1 showed the similar effect on the decrease in the Gpp (NH) p stimulated activity. Efaroxan, an I 1 imidazoline receptor antagonist, could partially reverse the inhibitory effect of clonidine on myocardial Gi? levels. Conclusion Clonidine can inhibit the elevation of myocardial Gi? levels, and the mechanisms of the inhibition may possibly be associated with the stimulatory effect of clonidine on I 1 imidazoline receptors.
ABSTRACT
Objective:To explore the roles of the caudal ventrolateral medulla(CVLM) in the central anti-hypertensive mechanism. Methods : In 20 urethane-anesthetized SD rats, the effects of I1-imidazoline receptor and ?2-adrenceptor antagonists (microinjection into the CVLM) on the cardiovascular responses induced by intravenous clonidine were observed. Results: Prior bilateral microinjection of mixed antagonist idazoxan (I1-imidazoline receptor and a2-adrenceptor) into the CVLM not only decreased the mean arterial pressure [(-17. 3 ? 6. 9) mmHg, 1 mmHg = 0. 133 kPa, P