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Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice.
Cardiovasc Res. 2005 Feb 01; 65(2):405-10.CR

Abstract

OBJECTIVE

Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a subset of sensory Adelta- and C-fiber afferents, has been suggested to play a beneficial role in myocardial ischemia. The aim of the present study was to investigate some receptors possibly involved in the proton-mediated CGRP release from the heart.

METHODS

CGRP release from freshly isolated hearts of mice lacking the capsaicin receptor (TRPV1-/-), the bradykinin receptor type 2 (B2-/-), or the acid-sensing ion channel type 3 (ASIC3-/-) and their wild-type littermates (TRPV1+/+, B2+/+, ASIC3+/+) were compared. Hearts were passed through a series of solutions based on oxygenated synthetic interstitial fluid (SIF). SIF buffered to pH 5.7 or 5.2 was used as an acidic test stimulus, and capsaicin (5x10(-7) M) was finally applied as a positive control. All eluates were processed using an enzyme immunoassay (EIA) for measurement of CGRP concentrations.

RESULTS

SIF at pH 5.7 and 5.2 caused significant increases in CGRP release in TRPV1+/+ but not in mice lacking the TRPV1 receptor. The same acid stimuli caused no significant differences in CGRP release between ASIC3+/+ and ASIC3-/- or between B2+/+ and B2-/-, respectively. Capsaicin caused massive CGRP release in all mouse genotypes with the exception of TRPV1-/-.

CONCLUSION

We conclude that cardiac acidosis is a strong stimulus to release CGRP from the mouse heart. This effect seems to be primarily mediated through activation of TRPV1 receptors that are known to be expressed by slowly conducting nociceptive primary afferent nerve fibers.

Authors+Show Affiliations

Department of Physiology and Experimental Pathophysiology, Friedrich-Alexander-University of Erlangen-Nuremberg, Universitätsstr. 17, D-91054 Erlangen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15639479

Citation

Strecker, Thomas, et al. "Role of Different Proton-sensitive Channels in Releasing Calcitonin Gene-related Peptide From Isolated Hearts of Mutant Mice." Cardiovascular Research, vol. 65, no. 2, 2005, pp. 405-10.
Strecker T, Messlinger K, Weyand M, et al. Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice. Cardiovasc Res. 2005;65(2):405-10.
Strecker, T., Messlinger, K., Weyand, M., & Reeh, P. W. (2005). Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice. Cardiovascular Research, 65(2), 405-10.
Strecker T, et al. Role of Different Proton-sensitive Channels in Releasing Calcitonin Gene-related Peptide From Isolated Hearts of Mutant Mice. Cardiovasc Res. 2005 Feb 1;65(2):405-10. PubMed PMID: 15639479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice. AU - Strecker,Thomas, AU - Messlinger,Karl, AU - Weyand,Michael, AU - Reeh,Peter W, PY - 2004/05/02/received PY - 2004/10/10/revised PY - 2004/10/13/accepted PY - 2005/1/11/pubmed PY - 2005/3/3/medline PY - 2005/1/11/entrez SP - 405 EP - 10 JF - Cardiovascular research JO - Cardiovasc Res VL - 65 IS - 2 N2 - OBJECTIVE: Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a subset of sensory Adelta- and C-fiber afferents, has been suggested to play a beneficial role in myocardial ischemia. The aim of the present study was to investigate some receptors possibly involved in the proton-mediated CGRP release from the heart. METHODS: CGRP release from freshly isolated hearts of mice lacking the capsaicin receptor (TRPV1-/-), the bradykinin receptor type 2 (B2-/-), or the acid-sensing ion channel type 3 (ASIC3-/-) and their wild-type littermates (TRPV1+/+, B2+/+, ASIC3+/+) were compared. Hearts were passed through a series of solutions based on oxygenated synthetic interstitial fluid (SIF). SIF buffered to pH 5.7 or 5.2 was used as an acidic test stimulus, and capsaicin (5x10(-7) M) was finally applied as a positive control. All eluates were processed using an enzyme immunoassay (EIA) for measurement of CGRP concentrations. RESULTS: SIF at pH 5.7 and 5.2 caused significant increases in CGRP release in TRPV1+/+ but not in mice lacking the TRPV1 receptor. The same acid stimuli caused no significant differences in CGRP release between ASIC3+/+ and ASIC3-/- or between B2+/+ and B2-/-, respectively. Capsaicin caused massive CGRP release in all mouse genotypes with the exception of TRPV1-/-. CONCLUSION: We conclude that cardiac acidosis is a strong stimulus to release CGRP from the mouse heart. This effect seems to be primarily mediated through activation of TRPV1 receptors that are known to be expressed by slowly conducting nociceptive primary afferent nerve fibers. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/15639479/Role_of_different_proton_sensitive_channels_in_releasing_calcitonin_gene_related_peptide_from_isolated_hearts_of_mutant_mice_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2004.10.013 DB - PRIME DP - Unbound Medicine ER -