TY - JOUR

T1 - Characterization of capsaicin induced responses in mice vas deferens

T2 - evidence of CGRP uptake

AU - Sheykhzade, Majid

AU - Gupta, Saurabh

AU - Sørensen, Tinne

AU - Sørensen, Ole Aabling

AU - Koch, Hans

AU - Boonen, Harrie C M

AU - Back, Ole

AU - Fjalland, Bjarne

N1 - Copyright © 2011. Published by Elsevier B.V.

PY - 2011

Y1 - 2011

N2 - 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)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]aCGRP>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.

AB - 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)]aCGRP~adrenomedullin (AM)>[Cys(ACM)(2,7)]aCGRP>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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.ejphar.2011.06.031

DO - 10.1016/j.ejphar.2011.06.031

M3 - Journal article

C2 - 21741970

VL - 667

SP - 375

EP - 382

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -