Johnston H, Majewski H
Br J Pharmacol. 1986 Mar;87(3):553-62. doi: 10.1111/j.1476-5381.1986.tb10197.x.
In rabbit isolated pulmonary artery previously incubated with [3H]-noradrenaline, isoprenaline (0.3 microM) had no effect on the stimulation-induced outflow of radioactivity. However, if the phosphodiesterase inhibitor ICI 63,197 (30 microM) or the alpha-adrenoceptor blocker phentolamine (1 microM) was present, then isoprenaline significantly enhanced the stimulation-induced outflow, an effect blocked by propranolol (0.1 microM). ICI 63,197 (30 microM) but not phentolamine significantly enhanced the stimulation-induced outflow of radioactivity. In mouse isolated atria previously incubated with [3H]-noradrenaline and stimulated at a frequency of 10 Hz, isoprenaline had no effect on the stimulation-induced outflow of radioactivity; this is in contrast to its release-enhancing effects at stimulation frequencies of 4 Hz and 2 Hz. The facilitation of stimulation-induced outflow by isoprenaline at 4 Hz was blocked by propranolol (0.08 microM) which, by itself, had no effect on the stimulation-induced outflow. At a stimulation frequency of 2 Hz in mouse atria the facilitatory effect of isoprenaline (0.01 microM) was significantly greater in the presence of ICI 63,197 (30 microM) which, by itself, had no effect on the stimulation-induced outflow. Similarly, the facilitatory effect of isoprenaline was significantly greater in the presence of phentolamine (1 microM) but, in this case, phentolamine significantly enhanced the stimulation-induced outflow. These results suggest that facilitatory prejunctional beta-adrenoceptors are present in both rabbit pulmonary artery and mouse atria. The effects of the phosphodiesterase inhibitor ICI 63,197 suggest that they are linked to adenylate cyclase in both tissues and we propose that the ability of phentolamine to facilitate the release and enhance the effect of isoprenaline may be due to the blockade of alpha-adrenoceptor inhibition of adenylate cyclase. This latter proposition needs further investigation.
在预先用[3H]-去甲肾上腺素孵育的兔离体肺动脉中，异丙肾上腺素（0.3微摩尔）对刺激诱导的放射性流出没有影响。然而，如果存在磷酸二酯酶抑制剂ICI 63,197（30微摩尔）或α-肾上腺素能受体阻滞剂酚妥拉明（1微摩尔），那么异丙肾上腺素会显著增强刺激诱导的流出，这一效应被普萘洛尔（0.1微摩尔）阻断。ICI 63,197（30微摩尔）而非酚妥拉明显著增强了刺激诱导的放射性流出。在预先用[3H]-去甲肾上腺素孵育并以10赫兹频率刺激的小鼠离体心房中，异丙肾上腺素对刺激诱导的放射性流出没有影响；这与其在4赫兹和2赫兹刺激频率下的释放增强作用形成对比。异丙肾上腺素在4赫兹时对刺激诱导流出的促进作用被普萘洛尔（0.08微摩尔）阻断，而普萘洛尔本身对刺激诱导的流出没有影响。在小鼠心房2赫兹的刺激频率下，在存在ICI 63,197（30微摩尔）的情况下，异丙肾上腺素（0.01微摩尔）的促进作用显著更大，而ICI 63,197本身对刺激诱导的流出没有影响。同样，在存在酚妥拉明（1微摩尔）的情况下，异丙肾上腺素的促进作用显著更大，但在这种情况下，酚妥拉明显著增强了刺激诱导的流出。这些结果表明，在兔肺动脉和小鼠心房中均存在促进性的突触前β-肾上腺素能受体。磷酸二酯酶抑制剂ICI 63,197的作用表明它们在两种组织中均与腺苷酸环化酶相关联，并且我们提出酚妥拉明促进释放并增强异丙肾上腺素作用的能力可能是由于阻断了α-肾上腺素能受体对腺苷酸环化酶的抑制。后一观点需要进一步研究。
