Corelease of neuropeptides from capsaicin-sensitive afferents dilates submucosal arterioles in guinea pig ileum.
Extrinsic sensory afferent nerves projecting to the guinea pig intestinal submucosal arterioles contain both substance P (SP) and calcitonin gene-related peptide (CGRP); selective stimulation of these nerves causes vasodilation. However, it is not known whether either or both of these neuropeptides may be responsible for this neurogenic vasodilation. To examine this question, the actions of selective SP and CGRP antagonists on vasodilations evoked by SP, CGRP, and selective stimulation of extrinsic sensory afferents with capsaicin were measured in isolated submucosal arteriolar preparations with videomicroscopy. The SP receptor antagonist CP-96,345 (200 nM) abolished the vasodilation produced by half-maximal concentration (EC50) of SP and was without effect on the vasodilation produced by EC50 concentration of CGRP. Conversely, the CGRP receptor antagonist, CGRP-(8--37) (1 microM) abolished the vasodilation to CGRP but did not alter the SP-induced vasodilation. Neither antagonist altered the muscarinic vasodilation or nerve-evoked sympathetic vasoconstriction. Maximum inhibition of the capsaicin-induced vasodilation by CP-96,345 (600 nM) was 67%, and maximum inhibition of this response by CGRP-(8--37) (2 microM) was 53%. Complete inhibition of the capsaicin-induced vasodilation occurred when both antagonists were present. It is concluded that the vasodilation in response to activation of extrinsic sensory afferents innervating submucosal arterioles is due to the corelease of SP and CGRP.
Vanner
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Department of Medicine, Queen's Universit, Kingston, Ontario, Canada.
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004347:Drug Interactions; D006168:Guinea Pigs; D007082:Ileum / Q000098:blood supply*; D007413:Intestinal Mucosa / Q000098:blood supply*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology*
D001713:Biphenyl Compounds; D009479:Neuropeptides; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; C066892:CP 96345