Selective stimulation of GalR1 and GalR2 in rat substantia gelatinosa reveals a cellular basis for the anti- and pro-nociceptive actions of galanin.
Galanin modulates spinal nociceptive processing by interacting with two receptors, GalR1 and GalR2. The underlying neurophysiological mechanisms were examined by whole-cell recording from identified neurons in the substantia gelatinosa of young adult rats. GalR1 was activated with a 'cocktail' containing the GalR1/2 agonist, AR-M 961 (0.5 microM), in the presence of the GalR2 antagonist, M871 (1.0-2.5 microM). GalR2 was activated with the selective agonist, AR-M 1896 (0.5-1.0 microM). Application of the 'GalR1 agonist cocktail' often activated an inwardly-rectifying conductance in delay firing (excitatory) and tonically firing (inhibitory) neurons. This conductance was not activated by AR-M 1896 which instead decreased or increased an outwardly-rectifying conductance at voltages positive to -70 mV. Despite this variability in its actions on current-voltage relationships, AR-M 1896 very consistently decreased membrane excitability, as measured by cumulative action potential latency in response to a depolarizing current ramp. This strong GalR2-mediated effect was seen in neurons where membrane conductance was decreased, and where membrane excitability might be predicted to increase. GalR2 was also located presynaptically, as AR-M 1896 increased the interevent interval of spontaneous EPSCs in both delay and tonic cells. By contrast, the 'GalR1 agonist cocktail' had little effect on spontaneous EPSCs, suggesting that presynaptic terminals do not express GalR1. These diverse actions of GalR1 and GalR2 activation on both inhibitory and excitatory neurons are discussed in relation to the known spinal antinociceptive and pro-nociceptive actions of galanin, to the possible association of GalR1 with the inhibitory G-protein, G(i/o) and to report that GalR2 activation suppresses Ca2+ channel currents.
Alier
Kwai A
KA
Department of Pharmacology, University of Alberta, 9.75 Medical Sciences Building, Edmonton, Alta., Canada T6G 2H7 Centre for Neuroscience, University of Alberta, Edmonton, Alta., Canada Department of Neurochemistry, Stockholm University, Stockholm 10691, Sweden.
Chen
Yishen
Y
Sollenberg
Ulla E
UE
Langel
Ülo
Ü
Smith
Peter A
PA
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019004:Galanin / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000819:agonists / Q000502:physiology*; D044092:Receptor, Galanin, Type 2 / Q000819:agonists / Q000502:physiology*; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D019004:Galanin