Quantitative autoradiographic localization of [125I-Tyr8]bradykinin receptor binding sites in the rat spinal cord: effects of neonatal capsaicin, noradrenergic deafferentation, dorsal rhizotomy and peripheral axotomy.
In vitro receptor autoradiography was used to localize, quantify and characterize [125I-Tyr8]bradykinin binding sites in all major spinal cord segments of normal rats and animals subjected to various chemical treatments and surgical lesions. [125I-Tyr8]bradykinin specific binding sites were predominantly located to superficial laminae of the rat dorsal horn, with the substantia gelatinosa showing the highest density of labelling (values ranging from 3.1 fmol/mg tissue in cervical to 4.5 fmol/mg tissue in lumbar segments). A moderate density (1.8-3.0 fmol/mg tissue) of specific binding was observed in lamina III, whereas in other areas, i.e. laminae I and IV-X, lower amounts of labelling were detected. Within the superficial laminae of the dorsal horn, [125I-Tyr8]bradykinin binding was largely distributed over the neurophil with some perikarya showing concentrations of labelling. In contrast, the ventral horn showed a rather homogeneous distribution of [125I-Tyr8]bradykinin binding over the neuropil, with silver grain alignments surrounding motoneuron perikaryas and proximal processes. Bradykinin, [Tyr8]bradykinin and B2 receptor antagonists (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (Hoe 140), D-Arg[Tyr3,D-Phe7,Leu8]bradykinin, D-Arg[Hyp3, Leu8]bradykinin, D-Arg[Hyp2, Thi5,8,-Phe7]bradykinin D-Arg[Hyp3, D-Phe7, Leu8]bradykinin, Tyr0, D-Arg[Hyp3, D-Phe7, Leu8]bradykinin inhibited [125I-Tyr8]-bradykinin binding with very high subnanomolar affinities, while the B1 receptor agonist (Tyr0,des-Arg10-kallidin) and antagonist ([Leu8]-des-Arg9-bradykinin) did not significantly affect [125I-Tyr8]bradykinin binding at up to micromolar concentrations. Two weeks after unilateral lumbar dorsal rhizotomy (L1-L6) or peripheral lesions of the sciatic nerve, significant decreases ( +/- 50%) in [125I-Tyr8]bradykinin binding sites were found in ipsilateral laminae I-III of lumbar spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
Lopes
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Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Kar
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Chrétien
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Regoli
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D
Quirion
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Couture
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R
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001369:Axons / Q000502:physiology; D001665:Binding Sites / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D016627:Oxidopamine; D010525:Peripheral Nerves / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism*; D019051:Rhizotomy; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000187:drug effects
D018002:Receptors, Bradykinin; C026201:bradykinin, Tyr-; D016627:Oxidopamine; D002211:Capsaicin; D001920:Bradykinin