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Focal Stimulation of the Mossy Fibers Releases Endogenous Dynorphins That Bind K1 ‐Opioid Receptors in Guinea Pig Hippocampus
Author(s) -
Wagner John J.,
Evans Christopher J.,
Chavkin Charles
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02132.x
Subject(s) - dynorphin , stimulation , chemistry , dentate gyrus , hippocampal formation , dynorphin a , perforant path , endogenous opioid , receptor , biophysics , opioid peptide , endocrinology , medicine , neuroscience , opioid , biochemistry , biology
Physiological release of endogenous opioids in guinea pig hippocampal slices was detected in an in vitro competition binding assay using [ 3 H]U69,593, a K1 ‐selective radioligand. Veratridine‐induced opioid release caused a decrease in [ 3 H]U69,593 binding that was blocked by either tetrodotoxin addition or the removal of calcium from the incubation buffer. Focal electrical stimulation of opioid pep‐tide‐containing afferent pathways resulted in a decrease in [ 3 H]U69,593 binding, whereas stimulation of a major afferent lacking endogenous opioid immunoreactivity had no effect. The addition of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione blocked the reduction in [ 3 H]U69,593 binding caused by perforant path stimulation, but not the reduction caused by mossy fiber stimulation, suggesting that the primary source of endogenous K ligands was likely to be the dentate granule cells. Antisera against dynorphin A(1–8) or dynorphin B peptides inhibited the effects of mossy fiber stimulation in the [ 3 H]U69,593 displacement assay. Antisera against other prodynorphin‐and proenkephalin‐derived opioid peptides had no effect. As shown by receptor autoradiography, the distribution of K1 binding sites was limited to the molecular layer of the dentate gyrus and the presubiculum region of temporal hippocampal slices. These results indicate that pro‐dynorphin‐derived opioids released under physiological conditions from the mossy fibers act at K1 receptors in the guinea pig dentate gyrus.