5-HT3 receptor antagonists inhibit sensory neuropeptide release from the rat spinal cord.
5-HT3 receptors may be present on primary afferent neurons containing substance P (SP), neurokinin A (NKA) or calcitonin gene-related peptide (CGRP). We investigated the release of SP-, NKA- and CGRP-immunoreactivities (IR) from rat spinal cord slices. Thirty mM potassium chloride caused an increased outflow of all three peptides, i.e. 140-190% of spontaneous release. This release was slightly enhanced in the presence of 3 x 10(-5) M 5-hydroxytryptamine (5-HT). In contrast, a significant inhibition of potassium-evoked, but not of basal NKA-IR and CGRP-IR release was observed when 10(-7) M BRL 43694 or ICS 205-930, two specific 5-HT3 receptor antagonists, were superfused together with 5-HT. In conclusion, 5-HT may facilitate the evoked release of peptides from central terminals of primary sensory neurons via 5-HT3 receptors.
Saria
A
A
Department of Psychiatry, University of Innsbruck Medical School, Austria.
Javorsky
F
F
Humpel
C
C
Gamse
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D017829:Granisetron; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015288:Neurokinin A / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D000077526:Tropisetron
D015740:Calcitonin Gene-Related Peptide; D017829:Granisetron; D007191:Indazoles; D007211:Indoles; D015288:Neurokinin A; D009479:Neuropeptides; D011188:Potassium; D012702:Serotonin Antagonists; D013373:Substance P; D000077526:Tropisetron