Involvement of neurokinins in antidromic vasodilatation in hairy and hairless skin of the rat hindlimb.
By intravenous application of the specific neurokininl receptor antagonist SR 140333 and the specific calcitonin gene-related peptide receptor antagonist CGRP8-37 we tested to what extent neurokinins (substance P, neurokinin A) and calcitonin gene-related peptide are involved in mediating antidromic vasodilatation in skin of anaesthetized Wistar rats. The lumbar sympathetic chain was sectioned bilaterally between ganglia L2 and L3 to remove ongoing vasoconstrictor activity to the hindquarter. The left dorsal root L5 was stimulated electrically at 1 Hz with 20 pulses supramaximal for activating C-fibres to evoke antidromic vasodilatation which was measured with laser Doppler flowmetry on the glabrous plantar skin and the hairy skin of the lower hindlimb within the left L5 territory. Stimulation-induced vasodilatation was tested after applying SR 140333 (0.1 mg/kg) and CGRP8-37 (0.3 mg/kg) alone or in combination. SR 140333 delayed the onset of the vasodilatation, but did not change its amplitude. CGRP8-37 reduced the amplitude and duration of the vasodilatation, but did not affect the latency of its onset. In combination, SR 140333 potentiated the effect of CGRP8-37 on the amplitude of the vasodilatation in glabrous but not in hairy skin and CGRP8-37 potentiated the delayed onset produced by SR 140333 in both cutaneous tissues. Antidromic vasodilatation in glabrous skin was almost totally blocked by SR 140333 (0.1 mg/kg) in combination with CGRP8-37 (0.45 mg/kg), but a substantial dilatation remained in hairy skin. It is concluded that in rat glabrous skin the vasodilatation evoked by a low level of activity in small-diameter primary afferents is likely to result from the release and synergistic action of neurokinins (substance P and/or neurokinin A) and calcitonin gene-related peptide, while in hairy skin neurokinins are involved to a minor extent only.
Häbler
H J
HJ
Physiologisches Institut, Christian-Albrechts-Universität, Kiel, Germany.
Timmermann
L
L
Stegmann
J U
JU
Jänig
W
W
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D006197:Hair / Q000502:physiology*; D006614:Hindlimb; D009412:Nerve Fibers / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000294:innervation*; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; C058636:calcitonin gene-related peptide (8-37); C085215:SR 140333; D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide