Role of Calcitonin Gene-Related Peptide in Inhibitory Neurotransmission to the Pig Bladder Neck

Martínez-Sáenz, Ana; Recio Visedo, María Paz; Orensanz, Luis M.; Leite Fernandes, Vitor Samuel; Martínez Sainz, María Del Pilar; Bustamante, Salvador; Carballido, Joaquín; García-Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente

Role of Calcitonin Gene-Related Peptide in Inhibitory Neurotransmission to the Pig Bladder Neck

Official URL

https://www.doi.org/10.1016/j.juro.2011.03.142

Publication date

2011

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URI

https://hdl.handle.net/20.500.14352/96084

Citation

Martínez-Sáenz A, Recio P, Orensanz LM, Fernandes VS, Martínez MP, Bustamante S, et al. Role of Calcitonin Gene-Related Peptide in Inhibitory Neurotransmission to the Pig Bladder Neck. Journal of Urology 2011;186:728–35. https://doi.org/10.1016/j.juro.2011.03.142.

Abstract

Purpose: We studied the role of calcitonin gene-related peptide in nonadrenergic, noncholinergic neurotransmission to the pig bladder neck. Materials and Methods: We used immunohistochemical techniques to determine the distribution of calcitonin gene-related peptide immunoreactive fibers as well as organ baths for isometric force recording. We investigated relaxation due to endogenously released or exogenously applied calcitonin gene-related peptide in urothelium denuded phenylephrine precontracted strips treated with guanethidine, atropine and NG-nitro-L-arginine to block noradrenergic neurotransmission, muscarinic receptors and nitric oxide synthase, respectively. Results: Rich calcitonin gene-related peptide immunoreactive innervation was found penetrating through the adventitia and distributed in the suburothelial and muscle layers. Numerous, variable size, varicose calcitonin gene-related peptide immunopositive terminals were seen close below the urothelium. In the muscle layer calcitonin gene-related peptide immunopositive nerves usually appeared as varicose terminals running along muscle fibers. Electrical field stimulation (2 to 16 Hz) and exogenous calcitonin gene-related peptide (0.1 nM to 0.3 μM) evoked frequency and concentration dependent relaxation, respectively. Nerve responses were potentiated by capsaicin, decreased by calcitonin gene-related peptide (8–37) and abolished by tetrodotoxin, capsaicin sensitive primary afferent blockers, calcitonin gene-related peptide receptors and neuronal voltage gated Na+ channels. Calcitonin gene-related peptide-induced relaxation was potentiated by the neuronal voltage gated Ca2+ channels blocker ω-conotoxin-GVIA and decreased by calcitonin gene-related peptide (8–37). Calcitonin gene-related peptide relaxation was not modified by blockade of endopeptidases, nitric oxide synthase, guanylyl cyclase and cyclooxygenase. Conclusions: Results suggest that calcitonin gene-related peptide is involved in the nonadrenergic, noncholinergic inhibitory neurotransmission of the pig bladder neck, producing relaxation through neuronal and muscle calcitonin gene-related peptide receptors. Nitric oxide/cyclic guanosine monophosphate and cyclooxygenase pathways do not seem to be involved in such responses.