Skip to main content
Log in

Interstitial cells of Cajal mediate excitatory sympathetic neurotransmission in guinea pig prostate

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Morphological and functional studies have confirmed that interstitial cells of Cajal (ICCs) are involved in many enteric motor neurotransmission pathways. Recent investigations have demonstrated that human and guinea pig prostate glands possess a distinct cell type with morphological and immunological similarities to ICCs. These prostate ICCs have a close relationship with nerve bundles and smooth muscle cells. Prostate smooth muscle tone is largely induced by stimulation from the sympathetic nervous system, which releases excitatory norepinephrine (NE) to act on the α1-adrenoceptor. We have performed morphological and functional experiments to determine the role of ICCs in sympathetic neurotransmission in the guinea pig prostate based on the hypothesis that prostate ICCs act as mediators of sympathetic neurotransmission. Immunohistochemistry revealed many close points of contact between ICCs and sympathetic nerve bundles and smooth muscle cells. Double-labeled sections revealed that α1-adrenoceptor and the gap junction protein connexin 43 were expressed in prostate ICCs. Surprisingly, prostate ICCs co-expressed tyrosine hydroxylase and dopamine β-hydroxylase, two markers of sympathetic neurons. Functionally, the application of NE evoked a large single inward current in isolated prostate ICCs in a dose-dependent manner. The inward current evoked by NE was mediated via the activation of α1-adrenoceptors, because it was abolished by the non-specific α-adrenoceptor antagonist, phentolamine and the specific α1-adrenoceptor antagonist, prazosin. Thus, ICCs in the guinea pig prostate are target cells for prostate sympathetic nerves and possess the morphological and functional characteristics required to mediate sympathetic signals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Arver S, Sjöstrand NO (1982) Functions of adrenergic and cholinergic nerves in canine effectors of seminal emission. Acta Physiol Scand 115:67–77

    Article  PubMed  CAS  Google Scholar 

  • Beckett EA, Takeda Y, Yanase H, Sanders KM, Ward SM (2005) Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach. J Comp Neurol 493:193–206

    Article  PubMed  CAS  Google Scholar 

  • Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM (1996) Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 93:12008–12013

    Article  PubMed  CAS  Google Scholar 

  • Davidson RA, McCloskey KD (2005) Morphology and localization of interstitial cells in the guinea-pig bladder: structural relationships with smooth muscle and neurons. J Urol 173:1385–1390

    Article  PubMed  Google Scholar 

  • Eckert RE, Schreier U, Drescher P, Madsen PO, Derouet H, Becht E, Steffens J, Ziegler M (1995) Regulation of prostatic smooth muscle contractility by intracellular second messengers: implications for the conservative treatment of benign prostatic hyperplasia. Urol Int 54:6–21

    Article  PubMed  CAS  Google Scholar 

  • Epperson A, Hatton WJ, Callaghan B, Doherty P, Walker RL, Sanders KM, Ward SM, Horowitz B (2000) Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol 279:C529–C539

    CAS  Google Scholar 

  • Exintaris B, Klemm MF, Lang RJ (2002) Spontaneous slow wave and contractile activity of the guinea pig prostate. J Urol 168:315–322

    Article  PubMed  Google Scholar 

  • Harrington AM, Hutson JM, Southwell BR (2005) Immunohistochemical localization of substance P NK1 receptor in guinea pig distal colon. Neurogastroenterol Motil 17:727–737

    Article  PubMed  CAS  Google Scholar 

  • Horiguchi K, Sanders KM, Ward SM (2003) Enteric motor neurons form synaptic-like junctions with interstitial cells of Cajal in the canine gastric antrum. Cell Tissue Res 311:299–313

    PubMed  Google Scholar 

  • Horowitz B, Ward SM, Sanders KM (1999) Cellular and molecular basis for electrical rhythmicity in gastrointestinal muscles. Annu Rev Physiol 61:19–43

    Article  PubMed  CAS  Google Scholar 

  • Huizinga JD, Thuneberg L, Klüppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349

    Article  PubMed  CAS  Google Scholar 

  • Iino S, Horiguchi K, Nojyo Y, Ward SM, Sanders KM (2009) Interstitial cells of Cajal contain signalling molecules for transduction of nitrergic stimulation in guinea pig caecum. Neurogastroenterol Motil 21:542–550

    Article  PubMed  CAS  Google Scholar 

  • Jun JY, Choi S, Yeum CH, Chang IY, You HJ, Park CK, Kim MY, Kong ID, Kim MJ, Lee KP, So I, Kim KW (2004) Substance P induces inward current and regulates pacemaker currents through tachykinin NK1 receptor in cultured interstitial cells of Cajal of murine small intestine. Eur J Phamacol 495:35–42

    Article  CAS  Google Scholar 

  • Kunisawa Y, Kawabe K, Niijima T, Honda K, Takenaka T (1985) A pharmacological study of alpha adrenergic receptor subtypes in smooth muscle of human urinary bladder base and prostatic uretha. J Urol 134:396–398

    PubMed  CAS  Google Scholar 

  • Lam M, Shigemasa Y, Exintaris B, Lang RJ, Hashitani H (2011) Spontaneous Ca2+ signaling of interstitial cells in the guinea pig prostate. J Urol 186:2478–2486

    Article  PubMed  CAS  Google Scholar 

  • Lavin ST, Southwell BR, Murphy R, Jenkinson KM, Furness JB (1998) Activation of neurokinin 1 receptors on interstitial cells of Cajal of the guinea-pig small intestine by substance P. Histochem Cell Biol 110:263–271

    Article  PubMed  CAS  Google Scholar 

  • Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K, Nishikawa S (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116:369–375

    PubMed  CAS  Google Scholar 

  • McCloskey KD, Gurney AM (2002) Kit-positive cells in the guinea pig bladder. J Urol 168:832–869

    Article  PubMed  Google Scholar 

  • Nemeth L, Puri P (2001) Three-dimensional morphology of c-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Lab Med 125:899–904

    PubMed  CAS  Google Scholar 

  • Nguyen DT, Dey A, Lang RJ, Ventura S, Exintaris B (2011) Contractility and pacemaker cells in the prostate gland. J Urol 185:347–351

    Article  PubMed  Google Scholar 

  • Ohkawa H (1983) Sympathetic neuromuscular transmission in the smooth muscle of guinea-pig prostate gland. Int J Fertil 28:68–77

    PubMed  CAS  Google Scholar 

  • Popescu LM, Gherghiceanu M, Cretoiu D, Radu E (2005) The connective connection: interstitial cells of Cajal (ICC) and ICC-like cells establish synapses with immunoreactive cells. Electron microscope study in situ. J Cell Mol Med 9:714–730

    Article  PubMed  CAS  Google Scholar 

  • Salmhofer H, Neuhuber WL, Ruth P, Huber A, Russwurm M, Allescher HD (2001) Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Morphological evidence. Cel1 Tissue Res 305:331–340

    Article  CAS  Google Scholar 

  • Sanders KM (1996) A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 111:492–515

    Article  PubMed  CAS  Google Scholar 

  • Seki K, Komuro T (2001) Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine. Cell Tissue Res 306:417–422

    Article  PubMed  CAS  Google Scholar 

  • Seki K, Zhou DS, Komuro T (1998) Immunohistochemical study of the c-kit expressing cells and connexin 43 in the guinea-pig digestive tract. J Auton Nerv Syst 68:182–187

    Article  PubMed  CAS  Google Scholar 

  • Seki N, Suzuki H (1989) Electrical and mechanical activity of rabbit prostate smooth muscles in response to nerve stimulation. J Physiol (Lond) 419:651–663

    CAS  Google Scholar 

  • Sergeant GP, Hollywood MA, McCloskey KD, Thornbury KD, McHale NG (2000) Specialised pacemaking cells in the rabbit urethra. J Physiol (Lond) 526:359–366

    Article  CAS  Google Scholar 

  • Sergeant GP, Hollywood MA, McCloskey KD, McHale NG, Thornbury KD (2001) Role of IP3 in modulation of spontaneous activity in pacemaker cells of rabbit urethra. Am J Physiol Cell Physiol 280:1349–1356

    Google Scholar 

  • Sergeant GP, Thornbury KD, McHale NG, Hollywood MA (2002) Characterization of norepinephrine-evoked inward currents in interstitial cells isolated from the rabbit urethra. Am J Physiol Cell Physiol 283:885–894

    Article  Google Scholar 

  • Shafik A, Shafik I, el-Sibai O (2005) Identification of c-kit-positive cells in the human prostate: the interstitial cells of Cajal. Arch Androl 51:345–351

    Article  PubMed  CAS  Google Scholar 

  • Spray DC, Bennett MV (1985) Physiology and pharmacology of gap junctions. Annu Rev Physiol 47:281–303

    Article  PubMed  CAS  Google Scholar 

  • Van der Aa F, Roskams T, Blyweert W, De Ridder D (2003) Interstitial cells in the human prostate: a new therapeutic target? Prostate 56:250–255

    Article  PubMed  Google Scholar 

  • Wang XY, Paterson C, Huizinga JD (2003) Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol Motil 15:531–543

    Article  PubMed  Google Scholar 

  • Wang YF, Daniel EE (2001) Gap junctions in gastrointestinal muscle contain multiple connexins. Am J Physiol Gastrointest Liver Physiol 281:533–543

    Google Scholar 

  • Ward SM, Morris G, Reese L, Wang XY, Sanders KM (1998) Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters. Gastroenterology 115:314–329

    Article  PubMed  CAS  Google Scholar 

  • Ward SM, Beckett EAH, Wang XY, Baker F, Khoyi M, Sanders KM (2000) Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci 20:1393–1403

    PubMed  CAS  Google Scholar 

  • Ward SM, Sanders KM, Hirst GD (2004) Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil 16:112–117

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qin-zhang Wang.

Additional information

This work was funded by The National Natural Science Foundation of China, project no. 81060064.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Jp., Ding, Gf. & Wang, Qz. Interstitial cells of Cajal mediate excitatory sympathetic neurotransmission in guinea pig prostate. Cell Tissue Res 352, 479–486 (2013). https://doi.org/10.1007/s00441-013-1572-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-013-1572-3

Keywords

Navigation