| SPFF, [2- (4-Amino-3-chloro-5-trifluomethyl-phenyl)-2-tert.-butylamino-ethanol chloride], was a newly synthesized β 2 adrenergic agonist by us. In this paper, we examined the bronchodilating effects, the receptorological characteristics and the action mechanism of this compound. And a part of safety evaluation work was also carried out.We studied in vitro the bronchodilating effects of SPFF and isoprenaline (ISO) on isolated guinea pig trachea strips with or without the precontraction of bronchocontractors (His and Ach). SPFF and isoprenaline dose-dependently decreased the resting tension of isolated guinea pig trachea strips with pD2 values of 7.66±0.68 and 8.79±0.19, respectively. SPFF also dose-dependently relaxed the isolated guinea pig trachea strip precontraction with His or Ach, and the maximum inhibition rate of the effects was 146 % and 82.6 %, respectively. Moreover, we confirmed that the bronchodilator effect of SPFF was due to the activation of β 2 adrenoceptor because this effect was easily antagonized by ICI-118551 (pA2 8.9010.01), a specific β 2 adrenoceptor antagonist. In addition, SPFF (3×10-3 -3×10-9mol.L-1) significantly inhibited the bronchoconstriction effect of histamine in isolated lung perfusion model in guinea pigs.The protective effects of SPFF and SAB on bronchospasm induced by bronchoconstrictor aerosol in guinea pigs in vivo were investigated, and the Konzett and Rossler experiment in rabbits in vivo was also performed. The results showed that SPFF significantly prolonged the latency time of histamine and acetylcholine induced asphyxiation collapse in guinea pigs: the ED50 value of SPFF i.g. was 0.32±0.05 mg/kgin this experiment. Meanwhile, the EDso values of SAB was 2.37±0.22, which meant that the bronchorelaxation effect of salbutamol was about 8 times less potent than that of SPFF in vivo. The result of the Konzett and Rossler experiment performed in anesthetized rabbits showed that intraduodenal administration of SPFF exerted an action of longer duration than salbutamol. SPFF (i.d) 20 , 40 , 80 ug/kg also significantly improved the alteration of lung compliance and resistance induced by His aerosol in anesthetized rabbits. From the results above we suggested that SPFF was a potent, long-acting bronchodilator with relatively higher β2 adrenoceptor selectivity. Moreover, SPFF(3×10-8 -3×10-6 mol.L-1) inhibited the release of histamine in ovalbumin-allergic rats lung fragments, which indicated a mast cell protection effect of this compound. In the investigation of the effect of SPFF on the mucus movement, it was shown that SPFF i.g 0.04,0.1, 0.25 mg/kg improved the cilium transportation function on the trachea of conscious pigeon while had no effect on the air way mucus excretion in mice, these results implied that, by prompting the clearance of airway, SPFF had an additional beneficial effect on the alleviation of asthma symptom.The positive chronotropic effects of SPFF in isolated guinea pig left atria (pD:2 , 5. 41±0. 38) was 2200 times less potent than that of ISO, and the B2AR selectivity index (log-1[pD2(trachea)-pD2(atria)]) obtained from function experiments was 178 and 1, respectively, for SPFF and ISO. Meanwhile, the selectivity index obtained from radio-ligand competitive assay using 3H-DHA for SPFF and ISO was 4.6 and 0.36, respectively. This result indicated that SPFF had a higher affinity to P2AR than ISO. As SPFF i.g (0.25, 0.5,1mg/kg) dramatically elevated the cAMP level in the lung tissue in rat, and significantly decreased the Ca2+ level in primary cultures of guinea pig trachea smooth muscle cells, we confirmed that the signal transduction pathway of SPFF should also be protein G - cAMP - Ca2+, which was the same as other p2 agonists. The desensitization characteristic of SPFF was studied in vitro and in vivo. In isolated guinea pig trachea strips, when incubated with SAB or SPFF at the concentration of 1×10-6 mol.L-1 for 1 h, severe tachyphylaxis was induced by SAB, meanwhile, SPFF did not induced tachy...
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