Co-localization of tachykinins and calcitonin gene-related peptide in capsaicin-sensitive afferents in relation to motility effects on the human ureter in vitro

Abstract

Tachykinin- and calcitonin gene-related peptide (CGRP) immunoreactivities were localized by immunohistochemistry in the same nerves of the kidney, renal pelvis and ureter as well as in spinal ganglion cells of both the guinea-pig and man. The tachykinin and CGRP-immunoreactive nerves in the ureter were present within the smooth muscle layers, around blood vessels, close to and within the lining epithelium. The levels of neurokinin A-, substance P- and CGRP-like immunoreactivity per tissue weight, as determined by radioimmunoassay, were about 30-100-fold higher in the guinea-pig than in the human ureter, which was in good agreement with the relative density of immunoreactive nerve fibres, as seen by immunohistochemistry. Capsaicin treatment caused an almost total disappearance of both neurokinin A-, substance P- and CGRP-immunoreactive nerve fibres in the guinea-pig ureter and a 90% depletion of neurokinin A, substance P- and CGRP-like immunoreactivity, further supporting a sensory origin of these nerves. Reversed-phase high performance liquid chromatography of water extracts of the human ureter revealed the presence of neurokinin A- and eledoisin-like material using antiserum K12, which does not cross-react with substance P. Most of the CGRP-like immunoreactivity in human ureter extracts co-eluted with synthetic human CGRP. Capsaicin both caused inhibition of spontaneous motility of the human ureter in vitro and initiated contractions in some preparations. Neurokinin A and neuropeptide K potently initiated phasic contractions of the ureter, while substance P had only minor contractile effects. CGRP inhibited both spontaneous and neurokinin A-induced ureteric contractions. In conclusion, peptides with potent opposite motility effects are present in the same, presumably sensory nerves of the ureter in both the guinea-pig and man. It will be of importance to determine whether local release of neuropeptides can account for ureteric motility changes accompanying sensory nerve activation upon ureteral obstruction, by e.g. renal calculi.

The Nitric Oxide Synthase/ Nitric Oxide and Heme Oxygenase/ Carbon Monoxide Pathways in the Human Ureter

“…This study disclosed few CGRP-IR nerves in the mucosa, sometimes co-running with nitrergic nerves. Such previously reported mucosal distribution [3] further emphasizes the sensory role of CGRP. Moreover, the overlap of NOS-containing innervation with the latter suggests that NO may also be an afferent messenger.…”

“…The sensory neuropeptide CGRP has been considered as a putative candidate for NANC inhibitory neurotransmission in the ureter of various species, including man [3]. This study disclosed few CGRP-IR nerves in the mucosa, sometimes co-running with nitrergic nerves.…”

“…Several transmitters may be involved in both excitatory and inhibitory neurotransmission [1, 2]. One of these transmitters, calcitonin gene-related peptide (CGRP), has been considered a likely candidate for NANC inhibitory neurotransmission in human ureteral smooth muscle [3], which does not exclude the participation of other mediators. Nitric oxide (NO) is an established mediator of NANC neurotransmission in various smooth muscles [4], and in the upper urinary tract, NO synthase (NOS)-immunoreactive (-IR) nerves have been demonstrated in the human ureter [5] and in the human [6, 7] and mouse [8] ureterovesical junction (UJV).…”

Interdependent Regulation of Afferent Renal Nerve Activity and Renal Function: Role of Transient Receptor Potential Vanilloid Type 1, Neurokinin 1, and Calcitonin Gene-Related Peptide Receptors

“…SP and CGRP are colocalized in renal pelvis sensory nerves and may be totally depleted after CAP treatment (Hua et al, 1987). CGRP perfused into the renal pelvis causes an increase in ARNA, which is blocked by a NK1 receptor antagonist .…”

Calcitonin Gene-Related Peptide (CGRP)-Immunoreactive Nerve Terminals in the Whole Mount Preparations of the Dog Urethra.

“…This nature was designated as "dendritic secretion" by FUJITA et al (1988). It has been recently shown that sensory neurons containing CGRP and SP in the genitourinary tract release these peptides from their dendrites after the application of capsaicin (HUA and LUNDBERG, 1986;HUA et al, 1987;AMANN et al, 1988;SANTICIOLI, et al, 1988). Concerning the mechanism of the dendritic secretion, i. e., "efferent" function of the afferent nerve fibers as proposed in peripheral SP/CGRP-containing nerve fibers, the following two hypotheses have been put forth (ISHIDA-YAMAMOTO and TOHYAMA, 1989): 1) A mechanism via an axon reflex; in which a free nerve ending receives stimulation, which is a conferred to an axon collateral to release signal substances from the varicose portion of the collateral.…”