Capsaicin induced afferent denervation and receptor-linked responses to CGRP in the rat.
We have examined the effect of neonatal capsaicin-induced destruction of primary afferent nerves in rats on the response to calcitonin gene-related peptide (CGRP) in vitro and in vivo. Denervation was confirmed by immunohistochemistry. Rat alpha-CGRP (rCGRP) activated adenylate cyclase in homogenates of rat spleen (basal activity 45 +/- 8.27, delta Vmax 75 +/- 16 pmol cyclic AMP min-1 protein; K(act) 2.04 +/- 0.44 nM). A single specific binding site for [125I]hCGRP was demonstrated in homogenates of spleen (Kd = 4.84 +/- 0.66 nM, Bmax = 1.43 +/- 0.35 pmol mg-1 protein). Neither adenylate cyclase activation nor binding site characteristics were affected by capsaicin-induced denervation. In addition, hypotensive responses to intravenous boluses of rCGRP were examined in anaesthetized rats. Neither the basal blood pressure nor the blood pressure fall in response to rCGRP were altered by neonatal denervation by capsaicin. In conclusion, there is no evidence of denervation hypersensitivity of receptor mediated responses to CGRP in vivo or in vitro, following capsaicin-induced denervation in the rat. This suggests that CGRP is unlikely to exert a sustained tonic influence on cardiovascular regulation in the rat.
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
J R
JR
McEwan
C
C
Newman
J
J
Wharton
J M
JM
Polak
J
J
MacDermot
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000502:physiology*; D013154:Spleen / Q000201:enzymology; D013562:Sympathectomy
D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin