Foster P S, Goldie R G, Paterson J W, Spina D
Br J Pharmacol. 1983 Dec;80(4):699-702. doi: 10.1111/j.1476-5381.1983.tb10060.x.
The relaxant potencies of (+/-)-isoprenaline and of (-)-noradrenaline (NA) in the pig isolated bronchus were increased 5.4 and 3.1 fold respectively by lowering the organ bath temperature from 37 degrees C to 27 degrees C, whereas the potencies of the non-catecholamine beta-adrenoceptor agonists fenoterol and orciprenaline were not significantly changed. At 37 degrees C, the catechol-O-methyl transferase (COMT) inhibitor U-0521 (30 microM), caused a 7.2 fold increase in the potency of isoprenaline but had no effect on the potency of fenoterol. At 27 degrees C the potency of isoprenaline was similar in the absence or presence of U-0521 (30 microM). Furthermore, in bronchi where extraneuronal uptake was inhibited by phenoxybenzamine, the potency of NA was not significantly altered by reducing bathing temperature from 37 degrees C to 27 degrees C. These results suggest that the hypothermic potentiation of isoprenaline in pig bronchus resulted from inhibition of COMT or of access to COMT, rather than from sensitization of beta 1-adrenoceptors.
将猪离体支气管的浴槽温度从37℃降至27℃时,(±)-异丙肾上腺素和(-)-去甲肾上腺素(NA)的舒张效能分别增加了5.4倍和3.1倍,而非儿茶酚胺β-肾上腺素能受体激动剂非诺特罗和奥西那林的效能则无显著变化。在37℃时,儿茶酚-O-甲基转移酶(COMT)抑制剂U-0521(30微摩尔)使异丙肾上腺素的效能增加了7.2倍,但对非诺特罗的效能无影响。在27℃时,无论有无U-05(30微摩尔),异丙肾上腺素的效能相似。此外,在苯氧苄胺抑制神经外摄取的支气管中,将浴槽温度从37℃降至27℃对NA的效能无显著影响。这些结果表明,猪支气管中异丙肾上腺素的低温增强作用是由于COMT受到抑制或无法接触到COMT,而非β1-肾上腺素能受体的敏感性增加所致。