DAMGO suppresses both excitatory and inhibitory synaptic transmission in supraoptic neurones of mouse hypothalamic slice preparations.
Opioid effects on synaptic transmission in the mouse supraoptic nucleus (SON) were investigated using whole-cell, patch-clamp techniques. The mu-opioid receptor agonist, [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) decreased the amplitude of both evoked excitatory postsynaptic currents (eEPSCs) and inhibitory postsynaptic currents (eIPSCs), and also decreased the frequency of both miniature EPSCs and IPSCs without effect on the amplitude. The selective mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2), and the nonselective antagonist naloxone, antagonized these inhibitory effects. The application of DAMGO suppressed the amplitude of both the first and second evoked postsynaptic currents with a paired-pulse stimulus protocol, but increased the paired-pulse ratios (second ePSC/first ePSC). DAMGO induced neither inward nor outward currents, and had no significant changes in either glutamate- or GABA-induced currents. When compared with the relatively selective kappa- and delta-opioid receptor agonists dynorphin and [D-Pen(2), D-Pen(5)]-enkephalin, DAMGO showed the most potent inhibitory effects on evoked and miniature postsynaptic currents. Taken together, these results imply that DAMGO strongly suppresses the release of glutamate and GABA via mu-opioid receptors in the mouse SON, and support the involvement of presynaptic regulation by opioids in the control of magnocellular neurosecretory neurones.
Honda
E
E
Department of Physiology, Kyushu Dental College, Kokurakitaku, Kitakyushu, Japan.
Ono
K
K
Inenaga
K
K
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011957:Receptors, Opioid / Q000819:agonists; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D009842:Oligopeptides; D011957:Receptors, Opioid; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-