Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice.
The endogenous opioid neurotransmitter beta-endorphin (beta-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any beta-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia. To further understand the cellular bases of these responses, we have studied mediobasal hypothalamic (MBH) neurons, including POMC neurons, using whole-cell patch recording in an in vitro slice preparation. Twenty-seven MBH cells were recorded in wild-type and 25 MBH cells were recorded in beta-END knockout mice. Neurons from both genotypes showed a significant positive correlation between DAMGO concentration (from 30 nM to 10 microM) and the induced outward K(+) current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC(50), or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing (3)H-DAMGO did not reveal any differences in total mu-opioid receptor binding between genotypes. Therefore, we conclude that the complete absence of beta-END throughout development did not alter either the expression of mu-opioid receptors or their coupling to K(+) channels in MBH neurons.
Slugg
R M
RM
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, USA.
Hayward
M D
MD
Ronnekleiv
O K
OK
Low
M J
MJ
Kelly
M J
MJ
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D012016:Reference Values; D001615:beta-Endorphin / Q000235:genetics / Q000502:physiology*
D018755:GABA Agonists; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D001418:Baclofen