Effect of bradykinin and prostaglandins on the release of calcitonin gene‐related peptide‐like immunoreactivity from the rat spinal cord in vitro

1 The release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) from the dorsal horn of the rat spinal cord in vitro in response to dorsal root stimulation was measured by radioimmunoassay. 2 Stimulation of the dorsal roots (3 or 4 roots on each side) at 10 Hz for 5 min evoked a mea...

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Bibliographic Details
Published in:British journal of pharmacology 1993-01, Vol.108 (1), p.185-190
Main Authors: Andreeva, L., Rang, H.P.
Format: Article
Language:English
Subjects:
1-Methyl-3-isobutylxanthine - pharmacology
Amino Acid Sequence
Animals
B2‐receptors
Biological and medical sciences
bradykinin
Bradykinin - analogs & derivatives
Bradykinin - antagonists & inhibitors
Bradykinin - pharmacology
Calcitonin Gene-Related Peptide - metabolism
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
CGRP release
Colforsin - pharmacology
cyclic AMP
Electric Stimulation
Female
Fundamental and applied biological sciences. Psychology
In Vitro Techniques
Indomethacin - pharmacology
Male
Molecular Sequence Data
prostaglandins
Prostaglandins - pharmacology
Radioimmunoassay
Rat spinal cord
Rats
Rats, Sprague-Dawley
Spinal Cord - drug effects
Spinal Cord - metabolism
Vertebrates: nervous system and sense organs
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Summary:1 The release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) from the dorsal horn of the rat spinal cord in vitro in response to dorsal root stimulation was measured by radioimmunoassay. 2 Stimulation of the dorsal roots (3 or 4 roots on each side) at 10 Hz for 5 min evoked a mean release (R1) of 134.3 ± 17.5 (n = 10) fmol CGRP‐LI; the release (R2) evoked by a second stimulation period 30 min later under control conditions was 77 ± 10% (n = 10) of R1. Test compounds were applied to the preparation following release R1, and their effect calculated from the value of R2/R1. 3 Bradykinin (0.01–10 μm) had no significant effect on the basal release of CGRP‐LI, but at 0.1–10 μm it increased 2–3 fold the release evoked by dorsal root stimulation. 4 This effect of bradykinin was prevented by indomethacin (10 μm), or by the B2‐receptor antagonist, Hoe140 (1–10 μm). In the presence of Hoe140, bradykinin significantly reduced R2/R1; the explanation for this is not clear. 5 The B1‐receptor agonist, Des‐Arg9‐bradykinin (10 μm), did not affect CGRP‐LI release nor was the effect of bradykinin blocked by the B1‐receptor antagonist, Des‐Arg9‐Leu8‐bradykinin (10 μm). 6 Various prostaglandins were found to mimic the effect of bradykinin on CGRP‐LI release. Their approximate order of potency was prostaglandin D2 (PGD2) = PGE1 > PGF2α = PGE2; PGI2 was ineffective at 10 μm. 7 Forskolin (30 μm) and 3‐isobutyl 1‐methylxanthine (IBMX; 10 μm) also increased the evoked release of CGRP‐LI. 8 It is concluded that bradykinin acts on B2‐receptors in the spinal cord, causing the formation of prostanoids, which in turn cause an enhancement of neuropeptide release from primary afferent nerve terminals in the dorsal horn. This effect may be secondary to activation of adenylate cyclase. Because B2‐receptors are mainly associated with primary afferent nerve terminals, it is likely that prostanoid production is also a function of these structures. Whether this action of bradykinin has any physiological function in nociceptive transmission remains unclear.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1993.tb13460.x