Bruce D S, Cope G W, Elam T R, Ruit K A, Oeltgen P R, Su T P
Department of Biology, Wheaton College, IL 60187.
Life Sci. 1987 Nov 2;41(18):2107-13. doi: 10.1016/0024-3205(87)90528-5.
Summer hibernation in ground squirrels (Citellus tridecemlineatus) can be induced by intravenous injection of hibernation-induction trigger (HIT) from winter bear plasma or its albumin fraction. In this study, we show that bear HIT depresses electrically-induced contraction of the guinea pig ileum myenteric plexus-longitudinal muscle preparation, and that naloxone, at 100, 1,000, or even 4,000 nM, fails to reverse that effect. In a simultaneous study, four sets of ground squirrels were implanted with osmotic minipumps which delivered solutions at a controlled and continuous rate. Two of the groups had pumps delivering naloxone at 1 mg/kg body weight per hour. The other two groups had saline-filled pumps (controls). One set of squirrels from each of the saline- and naloxone-filled pump groups were then injected intravenously with winter bear plasma. The remaining two groups of squirrels were injected with winter bear albumin fraction. Hibernation frequency was determined by measurements of core temperature (from surgically-implanted radio capsules), respiratory rate, and bouts of activity. Squirrels with saline-filled pumps hibernated four times more frequently than the naloxone groups. To confirm these findings, three squirrels from each naloxone group were reinjected with bear HIT after removal of the pumps. These six squirrels then hibernated over four times their previous frequency. Results suggest that bear HIT is not itself an opioid (since naloxone did not reverse bear HIT's depression of electrically-induced contraction of guinea pig ileum). The fact that bear HIT's effect of inducing summer hibernation in ground squirrels is effectively blocked in vivo by naloxone leads to the speculation that HIT may be either a precursor of endogenous opioids or a potent releaser of them, which, in turn, induce hibernation.
通过静脉注射来自冬眠熊血浆的冬眠诱导触发因子（HIT）或其白蛋白部分，可诱导地松鼠（Citellus tridecemlineatus）进行夏眠。在本研究中，我们发现熊HIT可抑制豚鼠回肠肌间神经丛 - 纵肌标本的电诱导收缩，并且纳洛酮在100、1000甚至4000 nM时都无法逆转这种作用。在一项同步研究中，四组地松鼠被植入渗透微型泵，这些泵以可控且持续的速率输送溶液。其中两组的泵输送每小时1 mg/kg体重的纳洛酮。另外两组的泵填充生理盐水（作为对照）。然后，从每组填充生理盐水和纳洛酮的泵组中各取一组地松鼠静脉注射冬眠熊血浆。其余两组地松鼠注射冬眠熊白蛋白部分。通过测量核心温度（来自手术植入的无线电胶囊）、呼吸频率和活动周期来确定冬眠频率。填充生理盐水泵的松鼠冬眠频率比纳洛酮组高四倍。为了证实这些发现，在移除泵后，给每个纳洛酮组的三只松鼠重新注射熊HIT。这六只松鼠随后的冬眠频率超过了之前的四倍。结果表明，熊HIT本身不是阿片类药物（因为纳洛酮不能逆转熊HIT对豚鼠回肠电诱导收缩的抑制作用）。纳洛酮在体内有效阻断熊HIT诱导地松鼠夏眠的作用这一事实，引发了一种推测，即HIT可能是内源性阿片类药物的前体或其强效释放剂，进而诱导冬眠。
