Inverse agonist is a new type of drug acting on receptors.Its research has experienced several stages, including discovery of ethylβ-carboline 3-carboxylate,activity study,proposal of the concept,two-state model,and constitutive activity theory in succession.Most G protein-coupled receptors possess constitutive activity,i.e.a proportion of receptors are in active state and can produce effects without any agonist.Inverse agonist has an affinity to receptors,but no intrinsic activity,so it cannot activate receptors.However,it can antagonize the constitutive activity of receptors,and produce an opposite effect on the corresponding agonist.Both agonist and inverse agonist can produce their effect alone with different mechanisms.Agonist activates its receptors,but inverse agonist antagonizes them.Both inverse agonist and antagonist can antagonize receptors.However,inverse agonist and antagonist antagonize the constitutive activity of receptor and the agonist’s effects,respectively.Inverse agonists can be used to treat diseases with enhanced constitutive activity,up-regulate and sensitize receptors with constitutive activity.Moreover,endogenous inverse agonists can maintain a specific physiological function.The study on inverse agonist has a theoretical significance in perfecting receptor theory as well as a clinical value in diagnosis and treatment of diseases with enhanced constitutive activity.

It was found that there were 31?s 13 ganglia or 1983 ?s 331 neurons ( n = 6) in canine right atrial ganglionated plexus (RAGP). Nicotine (100 ?g) was administered to the plexus in 30 anesthetized open-chest dogs. Either positive or negative inotropic and chronotropic responses were elicited. Control injections of 0. 1 m1 NS into RAGP and injections of nicotine (100 ?g and 200?g) did not elicite any cardiac responses. Following acute decentralzation of hearts, nicotine (100 ?g ) was againadministered to RAGP. Some positive and negative responses were still elicited, but frequency of the responses was reduced. It is concluded that nicotine can directly activate efferent sympathetic and parasympathetic neurons of RAGP. and indirectly activate them by stimulation of afferent neurons, these nicotine sensitive cardiac neurons can modulate cardiac function in ifferent tendencies.

Aim The present study was designed to investigate the contractile responses to vasoconstrictors in artery supplying colon carcinoma.Methods The artery supplying carcinoma was obtained from patients suffering from colonic carcinoma. The artery supplying carcinoma ambient normal tissue from patients with colon carcinoma and normal artery from patients with accident were used to control. Artery were cut into about 1 mm long cylindrical segments. The concentration-contractile curves induced by 4 vasoconstrictors were recorded. Results In the normal artery, the E_max and pEC_50 of contraction induced by noradrenaline (NA) were 97%?19% and 5.94?0.17(n=5), respectively; while in the artery supplying carcinoma, the E_max and pEC_50 of contraction induced by NA were 74%?5% and 5.54?0.21(n=5). In the artery supplying cancer ambient normal tissue, the E_max and pEC_50 of contraction induced by NA were 119%?11% and 5.84?0.09, respectively. The E_max in artery supplying carcinoma induced by NA was lower than that in normal arteries(P

Objective To study the protective effect of hydrogen sulfide(H2S) on intestinal ischemia-reperfusion(I/R) injury so as to provide a new clinical treatment on I/R.Methods NaHS was taken as a donor of H2S.Forty Sprague-Dawley rats were divided into 5 groups with 8 rats in each group: sham operation group,I/R model group,tetram ethylpyrazine group,and NaHS 7 ?mol/kg and 14 ?mol/kg groups.The contents of superoxidase dismutase(SOD),malondialdehyde(MDA) and glutathione peroxidase(GSH-Px) in serum and intestinal tissue were measured,respectively.The intestinal mucosal injury and histological alteration were observed.Results The content of MDA within serum and intestinal tissue was significantly reduced and the activities of SOD and GSH-Px were significantly increased.H2S could obviously reduce the injury in intestinal mucosa and glands.Conclusion H2S possesses a protective effect on intestinal I/R injury in rats.

Objective To investigate the possible protective effects of hydrogen sulfide (H2S) on rats with multiple organ dysfunction syndrome (MODS). Methods NaHS was taken as a donor of H2S. Forty Sprague-Dawley rats were divided into 5 groups with 8 rats in each group:sham group,MODS 12 h model group,MODS 24 h model group,NaHS protection 12 h and 24 h groups. The content of superoxidase dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-Px),alanime transaminse (ALT),creatine kinase (CK) and creatinine (Cr) in serum were measured,respectively. The histopathological changes in the heart,liver,lung,kidney and small intestine were observed. Results The serum content of SOD and GSH-Px was significantly higher in protected H2S groups (P

Effects of Cu2+,Zn2+and Mn2+ on responses to ACh were studied with toad rec-tus abdominis. Cu2+, Zn2+and Mn2+concentra-tion- dependently shifted the concentration-response curves for ACh to the right unparallelly and reduced the maximal response considerably. The pAh values of Cu2+ , Zn2+ and Mn2+ were 3.69, 2.95 and 2. 62, respectively. The inhibitory potent of Cu2+ and Zn2+ seemed to be 11.7 times and 2. 1 times respectively more thanthat of Mn2+. It was suggested that Cu2+, Zn2+ and Mn2+postsynaptically interfere with the action of ACh. However, Zn2+in lower concentration shifted the bottom section of the curve for ACh to the left and top, and shifted the top section of the curve to the right, suggesting that Mn2+in lower concentration be possessed of partial agonistic property.

Objective:To study the effects of nourishing yin and supplementing kidney of Peikun Capsule. Methods: The Kindney yin vacuity model was made with thyroid hormone. Results: It was found that Peikun Capsules could reduce the oxygen consumption, raise the pain threshold, lower the body temperature and increase water intake of mice with kidney yin vacuity. Conclusion: Peikun Capsule has obvious effects of nourishing yin and supplementing kidney.

AIM: To study the action of Pingkui Powder (Herba Gynostemmatis Pentaphylli, Fructus Hippophae, etc.) on the experimental acute gastric ulcer and its influence on gastric mucosa injury in rats. METHODS: The experimental models were established by means of histamine and indomethacin, area of ulcer was measured and quantity of gastric mucosa secretion of rats was analyzed. RESULTS: Pingkui Powder could reduce areas of ulcers, promote the gastric mucosa secretion. CONCLUSION: Pingkui Powder can improve the healing of acute ulcer and promote gastric mucosa secretion.

AIM: To observe the effect of Tongjingning Capsule (Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi, etc.) on reproductive organs of female immature mice and anti inflammatry analgesia. METHODS: Mouse uterus and ovaries were weighted. Mouse twisting numbers induced by acetic acid and mouse pain thresholds after heat stimulation were recorded. Swelling of mouse external ears, swelling of rat toes and rat granuloma were used for experiment models. RESULTS: Tongjingning Capsule significantly increased the weight of mouse uterus and ovaries. It could reduce mouse twisting numbers and prolong mouse pain thresholds after heat stimulation. It had inhibitory effects on swelling of mice's external ears resulted by dimethylbenzene, rat granuloma and swelling of rat toes resulted by egg white. CONCLUSION: Tongjingning Capsule can promote the growth of reproductive organs of female immature mice and ease pain and diminish inflammation.

Objective To observe the hemostatic effect of emergent hemostasis patch (EHP). Methods The coagulation time was studied with tube method in vitro. Hemostasis was studied with femoral artery hemorrhage models of rats and dogs as well as rabbit hepatorrhexis model in vivo. Results The clotting time of EHP of high, medium and low concentrations was (4.9±1.3)min, (5.7±1.8)min and (5.8±1.3)min, respectively, which was significantly lower than that of control (14.4±1.6)min in vitro. In femoral hemorrhage models of rats and dogs, the duration and amount of bleeding in EHP of high, medium and low doses were significantly decreased compared with those in the PVF sponge group (P<0.01 or P<0.05). The results of rabbit hepatorrhexis experiment showed that EHP of three doses obviously decreased the hemostatic time and blood loss compared with PVF sponge group (P<0.01). Conclusion EHP can shorten coagulation time and bleeding time, and reduce bleeding amount.