Substance P and calcitonin gene-related peptide immunoreactivity in nerves of the rat uterus: localization, colocalization and effects on uterine contractility.
Immunoreactivity to the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) was examined in nerves in the rat uterus as a prelude to studying their effects on uterine contractility. With immunocytochemical techniques, SP immunoreactivity (SP-I) and CGRP-I were localized in myometrial nerves throughout the uterine horns, with nerves immunoreactive for CGRP being the more numerous. Immunocytochemical double labeling studies revealed SP coexisted with CGRP in a subpopulation of CGRP-I nerve fibers, i.e., SP-I was not present in all CGRP-I nerves. Effects of these neuropeptides on uterine contractility were examined on in vitro preparations of uterine horns from diethylstilbestrol-treated rats. SP (10(-4) to 10(-8) M) stimulated uterine contraction in a dose-related manner. CGRP(1-37) and CGRP(8-37) had no effect on basal uterine tension. While CGRP(1-37) (10(-7) M) reduced SP-stimulated (10(-5) M) uterine contraction by 56%, CGRP(8-37) had no effect on SP-stimulated uterine contraction. However, CGRP(8-37) (10(-6) M) significantly reduced the ability of CGRP(1-37) (10(-7) M) to inhibit SP-stimulated uterine contraction. These results demonstrate that SP- and CGRP-I are present in, and coexist in some uterine nerves, presumably afferent nerves. The first 7 amino acids are necessary for the inhibitory effect of CGRP(1-37) on stimulated uterine contraction. In addition, CGRP(8-37) acted as an antagonist to this inhibitory action. SP and CGRP could be coreleased from afferent fibers in an "efferent fashion" and influence uterine contractility. SP having a contractile effect and CGRP having a relaxing effect.
Shew
R L
RL
University of Oklahoma, Department of Anatomical Sciences, Oklahoma City 73190.
Papka
R E
RE
McNeill
D L
DL
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000294:innervation* / Q000378:metabolism
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015740:Calcitonin Gene-Related Peptide