Premium
Agonists at μ‐opioid, M 2 ‐muscarinic and GABA B ‐receptors increase the same potassium conductance in rat lateral parabrachial neurones
Author(s) -
Christie M.J.,
North R.A.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11719.x
Subject(s) - muscarine , chemistry , lateral parabrachial nucleus , hyperpolarization (physics) , medicine , potassium channel , endocrinology , (+) naloxone , enkephalin , population , muscarinic acetylcholine receptor , gabab receptor , biophysics , membrane potential , agonist , receptor , parabrachial nucleus , opioid , biochemistry , biology , hypothalamus , stereochemistry , demography , sociology , nuclear magnetic resonance spectroscopy
1 Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro . 2 The membrane was hyperpolarized by the opioid peptides Tyr‐ d ‐Ala‐Gly‐MePhe‐Gly‐ol (DAGOL, 0.01–1μ m ) and [Met 5 ]enkephalin (3–30μ m ), though not by Tyr‐ d ‐Pen‐Gly‐Phe‐ d ‐Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively. 3 Baclofen (0.3–30 μ m ) also hyperpolarized the neurones; this action was unaffected by naloxone. 4 DAGOL, [Met 5 ]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration. 5 Muscarine has been shown previously to increase the potassium conductance by an action at M 2 ‐receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met 5 ]enkephalin were non‐additive, indicating that these agonists opened the same population of potassium channels. 6 Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential. 7 It is concluded that rat lateral parabrachial neurones express μ‐opioid, γ‐aminobutyric acid B (GABA B ), and M 2 ‐muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.