Kurz C M, Gottschalk C, Schlicker E, Kathmann M
Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, 53113 Bonn, Germany.
J Physiol Pharmacol. 2008 Mar;59(1):3-15.
We studied whether cannabinoid CB(1) receptors occur on the sympathetic neurones innervating the guinea-pig atrium and renal cortex. Atrial and cortical kidney pieces preincubated with [(3)H]-noradrenaline were superfused and the electrically (3 Hz)-evoked tritium overflow was examined. The evoked overflow in atrium was inhibited by the cannabinoid agonist WIN 55,212-2 maximally by 35%; its concentration-response curve was shifted to the right by the CB(1) antagonist rimonabant (pA(2) 8.3), which, by itself, did not affect the evoked overflow. The evoked overflow in the renal cortex was not altered by WIN 55,212-2. The muscarinic agonist oxotremorine and prostaglandin E(2) inhibited the evoked overflow maximally by 55 and 65% in atrium and by 80 and 55% in kidney, respectively. Furthermore, the nucleotide sequence of the guinea-pig CB(1) receptor was determined (GenBank DQ355990). The deduced amino acid sequence has a high homology to the corresponding sequence of man (98.7%) and rat or mouse (99.2%). In conclusion, presynaptic CB(1) receptors leading to inhibition of noradrenaline release occur in guinea-pig atrium but not renal cortex. The deduced amino acid sequence of the guinea-pig CB(1) receptor shows a homology of 99% to the CB(1) receptor sequence of rodents and humans.
我们研究了大麻素CB(1)受体是否存在于支配豚鼠心房和肾皮质的交感神经元上。将预先用[(3)H]-去甲肾上腺素孵育的心房和肾皮质切片进行灌流，并检测电刺激（3 Hz）诱发的氚外流。大麻素激动剂WIN 55,212-2可使心房诱发的外流最大抑制35%；其浓度-反应曲线被CB(1)拮抗剂利莫那班向右移动（pA(2) 8.3），利莫那班本身不影响诱发的外流。WIN 55,212-2对肾皮质诱发的外流无影响。毒蕈碱激动剂氧化震颤素和前列腺素E(2)分别使心房诱发的外流最大抑制55%和65%，使肾皮质诱发的外流最大抑制80%和55%。此外，还测定了豚鼠CB(1)受体的核苷酸序列（GenBank DQ355990）。推导的氨基酸序列与人（98.7%）、大鼠或小鼠（99.2%）的相应序列具有高度同源性。总之，导致去甲肾上腺素释放受抑制的突触前CB(1)受体存在于豚鼠心房而非肾皮质。豚鼠CB(1)受体推导的氨基酸序列与啮齿动物和人类的CB(1)受体序列具有99%的同源性。
