Effect of Endomorphins on the Activities of Hypothalamic Tuberoinfundibular Dopaminergic Neurons

• Main Authors: W. C. Chang, 張巍礩
• Other Authors: J. T. Pan, Ph.D.
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/22462291127896926717

碩士 === 國立陽明大學 === 生理學研究所 === 89 === The secretion of prolactin is inhibited by dopamine released from the tuberoinfundibular dopaminergic (TIDA) neurons. The cell bodies of these neurons are located in dorsomedial part of the hypothalamic arcuate nucleus (dmARN) and their axons terminate in the median eminence (ME). Various factors participate in the control of TIDA neurons, including the opioids and dopamine itself. Both opioid peptides and their receptors (mu and kappa subtype) are found in the ARN, and they are known to exhibit an inhibitory effect on TIDA neuronal activity. Endomorphin-1 and -2 (EM1/EM2) are newly discovered tetrapeptides that possess high affinity and selectivity for mu opiate receptor and exhibit potent analgesic effect. Immunohistochemical staining further demonstrates that EMs are located in the ARN. Thus, it was of interest to learn if EM1 and EM2 are involved in the opioidergic control of TIDA neurons. Both electrophysiological and neurochemical approaches were adopted in the study. Using extracellular single-unit recording of dmARN neurons in brain slices prepared from ovariectomized, estrogen-treated (OVX+E2) Sprague-Dawley rats, dmARN neurons that were inhibited by dopamine were selected first and then tested with EMs and naloxone, an opioid receptor antagonist. Of the 17 dopamine-responsive dmARN neurons, EM1 inhibited 100% of them, and its inhibitory effect could be prevented by co-administered naloxone (n=9). EM2 was tested in three dmARN neurons and it also exhibited 100% inhibition. Using intracerebroventricular injection in conscious OVX+E2 rats, EM1 and EM2 in 1 mg/rat dose inhibited TIDA neuronal activity(determined by DOPAC level in the ME) at 15-60 min, but the serum prolactin level was significantly increased only at 15 min. While EM2 in 0.1-5 mg/rat doses was effective in inhibiting the TIDA neurons, but the serum PRL only increased in 1and 5 mg/rat doses. EM1 did not exhibit a significant dose-dependent effect either. Co-administration of naloxone in 2.5 mg/rat dose significantly blocked the inhibitory effect of EM1 on TIDA neurons, and prevented the increase in serum PRL level. In summary, both in vitro electrophysiological and in vivo neurochemical data support the notion that EMs may play a significant inhibitory role in regulating the TIDA neuronal activity, and at the same time, it briefly stimulated the prolactin release.