Substance P in intervertebral discs. Binding sites on vascular endothelium of the human annulus fibrosus.
The annulus fibrosus of the human intervertebral disc is sparsely innervated, some of the fibers containing substance P. We could demonstrate, by autoradiography, binding sites for substance P localized on the endothelium of small blood vessels in the annulus fibrosus of human intervertebral discs removed during anterior fusion for back pain. In binding inhibition studies, binding of 125I-Bolton Hunter-substance P was inhibited by unlabeled substance P and the related tachykinins neurokinin A and neurokinin B with a rank order of potency substance P > NKA > NKB. Specific binding was reduced > 75 percent by 5'-guanylylimidodiphosphate, indicating G-protein coupling. These features are characteristic of an NK1 receptor through which vascular effects, i.e., vasodilation, plasma extravasation and angiogenesis of substance P, are mediated. The presence of NK1 receptors on blood vessels in the annulus fibrosus may indicate a role for substance P in tissue repair although acute proinflammatory effects may contribute to discogenic pain.
Ashton
I K
IK
Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopedic Hospital, Oswestry, UK.
Walsh
D A
DA
Polak
J M
JM
Eisenstein
S M
SM
D000328:Adult; D001665:Binding Sites; D004730:Endothelium, Vascular / Q000737:chemistry*; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000502:physiology; D006801:Humans; D007403:Intervertebral Disc / Q000098:blood supply* / Q000294:innervation; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D015288:Neurokinin A / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D015287:Neurokinin B / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000502:physiology; D013373:Substance P / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology
D007457:Iodine Radioisotopes; D018040:Receptors, Neurokinin-1; D013373:Substance P; D006165:Guanylyl Imidodiphosphate; D015288:Neurokinin A; D015287:Neurokinin B