Effect of neurokinins on canine prostate cell physiology.
BACKGROUND
Sensory peptide neurotransmitters have been implicated as significant regulators of prostate growth. This study was designed to evaluate the role of neurokinins in proliferation, differentiation, and contraction of canine prostate cells in culture.


METHODS
NK1, NK2, and NK3 receptor subtypes were localized in canine prostate tissue by immunocytochemistry and ligand binding studies. Functional effects of neurokinin agonists were tested on cell differentiation (expression of smooth muscle actin (SMA)), proliferation (MTS assay), and contraction of canine prostate cells in culture.


RESULTS
Immunocytochemical staining of canine prostate sections revealed strong stromal staining for NK1 together with weak stromal staining for NK2 and even weaker staining for NK3. Furthermore, there was overlapping localization of NK1 receptors, substance P (SP), and calcitonin gene-regulated peptide (CGRP) in prostate tissue sections. SP caused concentration-dependent increase in SMA expression that was attenuated in a concentration-dependent manner by YM-44778, a non-selective antagonist for neurokinin receptors, but not by either the NK2 antagonist (SR-48968) nor by the NK3 antagonist (SB-223412). SP and neurokinin A (NKA) also caused a modest contraction of stromal cells in collagen gels. NKA stimulated proliferation of prostate epithelial cells without any apoptotic effect, which was attenuated by SR-48968. Surprisingly, in binding studies NK3 appeared to be the most abundant neurokinin receptor subtype, although functional studies failed to reveal significant coupling of this receptor.


CONCLUSIONS
Our results suggest that, at least in vitro, neurokinins have modest effects on canine prostate epithelial cell proliferation, stromal differentiation, and contraction.
Walden
Paul D
PD
Department of Urology, NYU School of Medicine, New York, New York, USA.
Marinese
Dorene
D
Srinivasan
Dinesh
D
Tzoumaka
Elda
E
Syyong
Harley T
HT
Ford
Anthony P D W
AP
Bhattacharya
Anindya
A
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D011467:Prostate / Q000166:cytology* / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D011804:Quinolines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C109112:SB 222200; D014316:Tritium; D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide