title: Reciprocal sympatho-sensory control: functional role of nucleotides and calcitonin gene-related peptide in a peripheral neuroeffector junction.
abstract: The rat vas deferens has scattered sensory afferens plus a dense network of sympathetic motor efferens; these fibers are not known to interact functionally. We ascertained whether sensory fibers modulate the release of sympathetic transmitters through the release of calcitonin gene-related peptide (CGRP) and reciprocally assessed whether sympathetic transmitters modulate the overflow of ir-CGRP from sensory fibers. The tissue overflow of electrically evoked sympathetic co-transmitters (ATP/metabolites, noradrenaline (NA), and immunoreactive neuropeptide tyrosine (ir-NPY)) and the motor responses elicited were quantified following either exogenous CGRP or capsaicin application to elicit peptide release. Conversely, the outflow of ir-CGRP was examined in the presence of sympathetic transmitters. Exogenous CGRP reduced in a concentration-dependent manner the electrically evoked outflow of ATP/metabolites, NA, and ir-NPY with EC(50) values of 1.3, 0.18, and 1.9 nM, respectively. CGRP also reduced the basal NA overflow. The CGRP-evoked modulation was blocked by CGRP8-37 or H-89. Release of endogenous CGRP by capsaicin significantly reduced the basal overflow of NA, ir-NPY, and the electrically evoked sympathetic transmitter release. ADP, 2-methylthioadenosine-5'-O-diphosphate (2-MeSADP), or UTP decreased the electrically evoked ir-CGRP overflow, whereas clonidine, α,β-methyleneadenosine 5'-triphosphate (α,β-mATP), or adenosine (ADO) were inactive. CGRP acting postjunctionally also reduced the motor responses elicited by exogenous NA, ATP, or electrically evoked contractions. We conclude that CGRP exerts a presynaptic modulator role on sympathetic nerve endings and reciprocally ATP or related nucleotides influence the release of ir-CGRP from sensory fibers, highlighting a dynamic sympatho-sensory control between sensory fibers and sympathetic nerve ending. Postjunctional CGRP receptors further contribute to reduce the tissue sympathetic motor tone implying a pre and postjunctional role of CGRP as a sympathetic tone modulator.
authors.affiliation: Departamento de Fisiología, Laboratorio de Nucleótidos, Centro de Envejecimiento y Regeneración CARE, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
authors.forename: M V
authors.initials: MV
authors.lastname: Donoso
authors.forename: D
authors.initials: D
authors.lastname: Hermosilla
authors.forename: C
authors.initials: C
authors.lastname: Navarrete
authors.forename: P
authors.initials: P
authors.lastname: Álvarez
authors.forename: J G
authors.initials: JG
authors.lastname: Lillo
authors.forename: J P
authors.initials: JP
authors.lastname: Huidobro-Toro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D008297:Male; D009451:Neuroeffector Junction / Q000502:physiology*; D009711:Nucleotides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D009711:Nucleotides; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide