Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5520
Zeilhofer, H U; Muth-Selbach, U; Guhring, H; Erb, K; Ahmadi, S (2000). Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn. Journal of Neuroscience, 20(13):4922-4929.
Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two recently identified neuropeptides with opposing effects on several CNS functions, including spinal nociception. The cellular mechanisms that underlie this antagonism are not known. Here, we have investigated the effects of both peptides on synaptic transmission mediated by the three fast neurotransmitters l-glutamate, glycine, and GABA in the superficial layers of the rat spinal cord horn, which constitute the first important site of integration of nociceptive information in the pain pathway. NST selectively reduced transmitter release from inhibitory interneurons via a presynaptic Bordetella pertussis toxin-sensitive mechanism but left excitatory glutamatergic transmission unaffected. In contrast, N/OFQ only inhibited excitatory transmission. In the rat formalin test, an animal model of tonic pain in which N/OFQ exerts antinociceptive activity, NST induced profound hyperalgesia after intrathecal application. Similar to glycine and GABA(A) receptor antagonists, NST had no significant effects in the rat tail-flick test, a model of acute thermal pain. Our results provide a cellular basis for the antagonism of N/OFQ and NST and suggest the existence of a so far unidentified membrane receptor for NST. In addition, they support a role of NST as an endogenous inhibitor of glycinergic and GABAergic neurotransmission in the sensory part of the spinal cord and as a mediator of spinal hyperalgesia.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Pharmacology and Toxicology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||01 July 2000|
|Deposited On:||27 Mar 2009 08:17|
|Last Modified:||27 Nov 2013 19:48|
|Publisher:||Society for Neuroscience|
|Additional Information:||Holder of copyright: The Society for Neuroscience|
|Citations:||Web of Science®. Times cited: 57|
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