title: Characterization of capsaicin induced responses in mice vas deferens: evidence of CGRP uptake.
abstract: Calcitonin gene-related peptide (CGRP) is extensively distributed in primary afferent sensory nerves, including those innervating the genitourinary tract. Capsaicin can stimulate the release of CGRP from intracellular stores of these nerves, but this phenomenon has not been investigated in-depth in isolated preparations. The present study sets out to study and characterize the capsaicin as well as CGRP-induced responses in isolated mouse vas deferens. The effects of capsaicin and CGRP family of peptides were studied on electrically-induced twitch responses in the absence or presence of transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1) antagonist and CGRP receptor antagonists. Twitch responses were attenuated by capsaicin (1nM-30nM) and CGRP family of peptides. The potency order was CGRP>intermedin-long (IMDL)~[Cys(Et)(2,7)]αCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]αCGRP>amylin (AMY). These responses were disinhibited by the CGRP receptor antagonists and TRPV1 antagonists. The addition of CGRP receptor antagonists caused a transient potentiation of the twitch response and this potentiation was blocked by pretreatment with capsaicin and enhanced by incubation with exogenous CGRP. During the second consecutive cumulative concentration-response curve with capsaicin, the first phase of concentration-response curve disappeared and this was partially restored when the mouse vas deferens was preincubated with CGRP, suggesting the uptake of exogenous CGRP by nerves. Besides showing capsaicin-induced CGRP releases this study shows that exogenous CGRP can be taken up in vas deferens and can be re-released. CGRP uptake will add another dimension in understanding the homeostasis of this neuropeptide.
authors: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors: Majid
authors: M
authors: Sheykhzade
authors: Saurabh
authors: S
authors: Gupta
authors: Tinne
authors: T
authors: Sørensen
authors: Ole Aabling
authors: OA
authors: Sørensen
authors: Hans
authors: H
authors: Koch
authors: Harrie C M
authors: HC
authors: Boonen
authors: Ole
authors: O
authors: Back
authors: Bjarne
authors: B
authors: Fjalland
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin