Abstract
The projections of different subpopulations of myenteric neurons in the mouse small and large intestine were examined by combining immunohistological techniques with myotomy and myectomy operations. The myotomies were used to examine the polarity of neurons projecting within the myenteric plexus and showed that neurons containing immunoreactivity for nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), calbindin and 5-HT projected anally, while neurons with substance P (SP)-immunoreactivity projected orally, in both the small and large intestine. Neurons containing neuropeptide Y (NPY)- and calretinin-immunoreactivity projected locally. In the large intestine, GABA-immunoreactive neurons projected both orally and anally, with more axons tending to project anally. Myectomy operations revealed that circular muscle motor neurons containing NOS/VIP/±NPY and calretinin neurons projected anally both in the small and large intestine, while SP-immunoreactive circular muscle motor neurons projected orally. In the large intestine, GABA-IR circular muscle motor neurons projected both orally and anally. This study showed that although some neurons, such as the NOS/VP inhibitory motor neurons and interneurons, SP excitatory motor neurons and 5-HT interneurons had similar projections to those in other species, the projections of other chemical classes of neurons in the mouse intestine differed from those reported in other species.
Keywords: Enteric nervous system, calcium binding protein, neuropeptides, nitric oxide synthase
Full Text
The Full Text of this article is available as a PDF (854.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barbiers M., Timmermans J. P., Adriansen D., De Groodt-Lasseel M. H., Scheuermann D. W. Projections of neurochemically specified neurons in the porcine colon. Histochem Cell Biol. 1995 Feb;103(2):115–126. doi: 10.1007/BF01454008. [DOI] [PubMed] [Google Scholar]
- Barthó L., Holzer P. Search for a physiological role of substance P in gastrointestinal motility. Neuroscience. 1985 Sep;16(1):1–32. doi: 10.1016/0306-4522(85)90043-0. [DOI] [PubMed] [Google Scholar]
- Brookes S. J., Song Z. M., Ramsay G. A., Costa M. Long aboral projections of Dogiel type II, AH neurons within the myenteric plexus of the guinea pig small intestine. J Neurosci. 1995 May;15(5 Pt 2):4013–4022. doi: 10.1523/JNEUROSCI.15-05-04013.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brookes S. J., Steele P. A., Costa M. Calretinin immunoreactivity in cholinergic motor neurones, interneurones and vasomotor neurones in the guinea-pig small intestine. Cell Tissue Res. 1991 Mar;263(3):471–481. doi: 10.1007/BF00327280. [DOI] [PubMed] [Google Scholar]
- Brookes S. J., Steele P. A., Costa M. Identification and immunohistochemistry of cholinergic and non-cholinergic circular muscle motor neurons in the guinea-pig small intestine. Neuroscience. 1991;42(3):863–878. doi: 10.1016/0306-4522(91)90050-x. [DOI] [PubMed] [Google Scholar]
- Costa M., Furness J. B., Llewellyn-Smith I. J., Cuello A. C. Projections of substance P-containing neurons within the guinea-pig small intestine. Neuroscience. 1981;6(3):411–424. doi: 10.1016/0306-4522(81)90134-2. [DOI] [PubMed] [Google Scholar]
- Costa M., Furness J. B., Pompolo S., Brookes S. J., Bornstein J. C., Bredt D. S., Snyder S. H. Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. Neurosci Lett. 1992 Dec 14;148(1-2):121–125. doi: 10.1016/0304-3940(92)90819-s. [DOI] [PubMed] [Google Scholar]
- Costa M., Furness J. B. The origins, pathways and terminations of neurons with VIP-like immunoreactivity in the guinea-pig small intestine. Neuroscience. 1983 Apr;8(4):665–676. doi: 10.1016/0306-4522(83)90002-7. [DOI] [PubMed] [Google Scholar]
- Cuello A. C., Galfre G., Milstein C. Detection of substance P in the central nervous system by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3532–3536. doi: 10.1073/pnas.76.7.3532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daniel E. E., Furness J. B., Costa M., Belbeck L. The projections of chemically identified nerve fibres in canine ileum. Cell Tissue Res. 1987 Feb;247(2):377–384. doi: 10.1007/BF00218319. [DOI] [PubMed] [Google Scholar]
- Domoto T., Bishop A. E., Oki M., Polak J. M. An in vitro study of the projections of enteric vasoactive intestinal polypeptide-immunoreactive neurons in the human colon. Gastroenterology. 1990 Apr;98(4):819–827. doi: 10.1016/0016-5085(90)90003-j. [DOI] [PubMed] [Google Scholar]
- Ekblad E., Alm P., Sundler F. Distribution, origin and projections of nitric oxide synthase-containing neurons in gut and pancreas. Neuroscience. 1994 Nov;63(1):233–248. doi: 10.1016/0306-4522(94)90019-1. [DOI] [PubMed] [Google Scholar]
- Ekblad E., Ekman R., Håkanson R., Sundler F. Projections of peptide-containing neurons in rat colon. Neuroscience. 1988 Nov;27(2):655–674. doi: 10.1016/0306-4522(88)90296-5. [DOI] [PubMed] [Google Scholar]
- Ekblad E., Håkanson R., Sundler F. VIP and PHI coexist with an NPY-like peptide in intramural neurones of the small intestine. Regul Pept. 1984 Dec;10(1):47–55. doi: 10.1016/0167-0115(84)90052-1. [DOI] [PubMed] [Google Scholar]
- Ekblad E., Winther C., Ekman R., Håkanson R., Sundler F. Projections of peptide-containing neurons in rat small intestine. Neuroscience. 1987 Jan;20(1):169–188. doi: 10.1016/0306-4522(87)90010-8. [DOI] [PubMed] [Google Scholar]
- Fontaine J., Grivegnee A., Reuse J. Adrenoceptors and regulation of intestinal tone in the isolated colon of the mouse. Br J Pharmacol. 1984 Feb;81(2):231–243. doi: 10.1111/j.1476-5381.1984.tb10070.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furness J. B., Costa M. Neurons with 5-hydroxytryptamine-like immunoreactivity in the enteric nervous system: their projections in the guinea-pig small intestine. Neuroscience. 1982 Feb;7(2):341–349. doi: 10.1016/0306-4522(82)90271-8. [DOI] [PubMed] [Google Scholar]
- Furness J. B., Costa M. Projections of intestinal neurons showing immunoreactivity for vasoactive intestinal polypeptide are consistent with these neurons being the enteric inhibitory neurons. Neurosci Lett. 1979 Dec;15(2-3):199–204. doi: 10.1016/0304-3940(79)96113-5. [DOI] [PubMed] [Google Scholar]
- Furness J. B., Lloyd K. C., Sternini C., Walsh J. H. Projections of substance P, vasoactive intestinal peptide and tyrosine hydroxylase immunoreactive nerve fibres in the canine intestine, with special reference to the innervation of the circular muscle. Arch Histol Cytol. 1990 May;53(2):129–140. doi: 10.1679/aohc.53.129. [DOI] [PubMed] [Google Scholar]
- Furness J. B., Trussell D. C., Pompolo S., Bornstein J. C., Maley B. E., Storm-Mathisen J. Shapes and projections of neurons with immunoreactivity for gamma-aminobutyric acid in the guinea-pig small intestine. Cell Tissue Res. 1989;256(2):293–301. doi: 10.1007/BF00218886. [DOI] [PubMed] [Google Scholar]
- Furness J. B., Trussell D. C., Pompolo S., Bornstein J. C., Smith T. K. Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections. Cell Tissue Res. 1990 May;260(2):261–272. doi: 10.1007/BF00318629. [DOI] [PubMed] [Google Scholar]
- Furness J. B., Young H. M., Pompolo S., Bornstein J. C., Kunze W. A., McConalogue K. Plurichemical transmission and chemical coding of neurons in the digestive tract. Gastroenterology. 1995 Feb;108(2):554–563. doi: 10.1016/0016-5085(95)90086-1. [DOI] [PubMed] [Google Scholar]
- Gershon M. D., Chalazonitis A., Rothman T. P. From neural crest to bowel: development of the enteric nervous system. J Neurobiol. 1993 Feb;24(2):199–214. doi: 10.1002/neu.480240207. [DOI] [PubMed] [Google Scholar]
- Grider J. R. Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis. Am J Physiol. 1993 Feb;264(2 Pt 1):G334–G340. doi: 10.1152/ajpgi.1993.264.2.G334. [DOI] [PubMed] [Google Scholar]
- Hosoda K., Hammer R. E., Richardson J. A., Baynash A. G., Cheung J. C., Giaid A., Yanagisawa M. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell. 1994 Dec 30;79(7):1267–1276. doi: 10.1016/0092-8674(94)90017-5. [DOI] [PubMed] [Google Scholar]
- Hoyle C. H., Knight G. E., Burnstock G. Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. Br J Pharmacol. 1990 Mar;99(3):617–621. doi: 10.1111/j.1476-5381.1990.tb12979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huizinga J. D., Thuneberg L., Klüppel M., Malysz J., Mikkelsen H. B., Bernstein A. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995 Jan 26;373(6512):347–349. doi: 10.1038/373347a0. [DOI] [PubMed] [Google Scholar]
- Jin J. G., Katsoulis S., Schmidt W. E., Grider J. R. Inhibitory transmission in tenia coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors. J Pharmacol Exp Ther. 1994 Aug;270(2):433–439. [PubMed] [Google Scholar]
- Kapur R. P., Yost C., Palmiter R. D. A transgenic model for studying development of the enteric nervous system in normal and aganglionic mice. Development. 1992 Sep;116(1):167–175. doi: 10.1242/dev.116.Supplement.167. [DOI] [PubMed] [Google Scholar]
- Maccarrone C., Jarrott B. Differences in regional brain concentrations of neuropeptide Y in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Brain Res. 1985 Oct 14;345(1):165–169. doi: 10.1016/0006-8993(85)90848-0. [DOI] [PubMed] [Google Scholar]
- Maley B., Newton B. W. Immunohistochemistry of gamma-aminobutyric acid in the cat nucleus tractus solitarius. Brain Res. 1985 Mar 25;330(2):364–368. doi: 10.1016/0006-8993(85)90699-7. [DOI] [PubMed] [Google Scholar]
- McConalogue K., Furness J. B. Projections of nitric oxide synthesizing neurons in the guinea-pig colon. Cell Tissue Res. 1993 Mar;271(3):545–553. doi: 10.1007/BF02913739. [DOI] [PubMed] [Google Scholar]
- McConalogue K., Low A. M., Williamson S., Bornstein J. C., Furness J. B. Calretinin-immunoreactive neurons and their projections in the guinea-pig colon. Cell Tissue Res. 1994 May;276(2):359–365. doi: 10.1007/BF00306121. [DOI] [PubMed] [Google Scholar]
- Messenger J. P., Furness J. B. Projections of chemically-specified neurons in the guinea-pig colon. Arch Histol Cytol. 1990 Dec;53(5):467–495. doi: 10.1679/aohc.53.467. [DOI] [PubMed] [Google Scholar]
- Messenger J. P. Immunohistochemical analysis of neurons and their projections in the proximal colon of the guinea-pig. Arch Histol Cytol. 1993 Dec;56(5):459–474. doi: 10.1679/aohc.56.459. [DOI] [PubMed] [Google Scholar]
- Murphy S., Li Z. S., Furness J. B., Campbell G. Projections of nitric oxide synthase- and peptide-containing neurons in the small and large intestines of the toad (Bufo marinus). J Auton Nerv Syst. 1994 Jan-Feb;46(1-2):75–92. doi: 10.1016/0165-1838(94)90146-5. [DOI] [PubMed] [Google Scholar]
- Okasora T., Bywater R. A., Taylor G. S. Projections of enteric motor neurons in the mouse distal colon. Gastroenterology. 1986 Jun;90(6):1964–1971. doi: 10.1016/0016-5085(86)90268-4. [DOI] [PubMed] [Google Scholar]
- Puffenberger E. G., Hosoda K., Washington S. S., Nakao K., deWit D., Yanagisawa M., Chakravart A. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell. 1994 Dec 30;79(7):1257–1266. doi: 10.1016/0092-8674(94)90016-7. [DOI] [PubMed] [Google Scholar]
- Rogers J. H. Immunoreactivity for calretinin and other calcium-binding proteins in cerebellum. Neuroscience. 1989;31(3):711–721. doi: 10.1016/0306-4522(89)90435-1. [DOI] [PubMed] [Google Scholar]
- Sanders K. M., Ward S. M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992 Mar;262(3 Pt 1):G379–G392. doi: 10.1152/ajpgi.1992.262.3.G379. [DOI] [PubMed] [Google Scholar]
- Sang Q., Young H. M. Chemical coding of neurons in the myenteric plexus and external muscle of the small and large intestine of the mouse. Cell Tissue Res. 1996 Apr;284(1):39–53. doi: 10.1007/s004410050565. [DOI] [PubMed] [Google Scholar]
- Stark M. E., Szurszewski J. H. Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology. 1992 Dec;103(6):1928–1949. doi: 10.1016/0016-5085(92)91454-c. [DOI] [PubMed] [Google Scholar]
- Sundler F., Ekblad E., Håkanson R. Projections of enteric peptide-containing neurons in the rat. Arch Histol Cytol. 1989;52 (Suppl):181–189. doi: 10.1679/aohc.52.suppl_181. [DOI] [PubMed] [Google Scholar]
- Timmermans J. P., Barbiers M., Scheuermann D. W., Stach W., Adriaensen D., Mayer B., De Groodt-Lasseel M. H. Distribution pattern, neurochemical features and projections of nitrergic neurons in the pig small intestine. Ann Anat. 1994 Dec;176(6):515–525. doi: 10.1016/s0940-9602(11)80387-0. [DOI] [PubMed] [Google Scholar]
- Uemura S., Pompolo S., Furness J. B. Colocalization of neuropeptide Y with other neurochemical markers in the guinea-pig small intestine. Arch Histol Cytol. 1995 Dec;58(5):523–536. doi: 10.1679/aohc.58.523. [DOI] [PubMed] [Google Scholar]
- Unekwe P. C., Savage A. O. The effects of electrical stimulation, adenosine and adenosine-5'-triphosphate (ATP) on mouse rectal muscle. Pharmacol Res. 1991 May;23(4):389–398. doi: 10.1016/1043-6618(91)90053-z. [DOI] [PubMed] [Google Scholar]
- Ward S. M., Burns A. J., Torihashi S., Sanders K. M. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994 Oct 1;480(Pt 1):91–97. doi: 10.1113/jphysiol.1994.sp020343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward S. M., Xue C., Sanders K. M. Localization of nitric oxide synthase in canine ileocolonic and pyloric sphincters. Cell Tissue Res. 1994 Mar;275(3):513–527. doi: 10.1007/BF00318820. [DOI] [PubMed] [Google Scholar]
- Wardell C. F., Bornstein J. C., Furness J. B. Projections of 5-hydroxytryptamine-immunoreactive neurons in guinea-pig distal colon. Cell Tissue Res. 1994 Nov;278(2):379–387. doi: 10.1007/BF00414180. [DOI] [PubMed] [Google Scholar]
- Wattchow D. A., Brookes S. J., Costa M. The morphology and projections of retrogradely labeled myenteric neurons in the human intestine. Gastroenterology. 1995 Sep;109(3):866–875. doi: 10.1016/0016-5085(95)90396-8. [DOI] [PubMed] [Google Scholar]
- Williamson S., Pompolo S., Furness J. B. GABA and nitric oxide synthase immunoreactivities are colocalized in a subset of inhibitory motor neurons of the guinea-pig small intestine. Cell Tissue Res. 1996 Apr;284(1):29–37. doi: 10.1007/s004410050564. [DOI] [PubMed] [Google Scholar]
- Young H. M., Furness J. B. Ultrastructural examination of the targets of serotonin-immunoreactive descending interneurons in the guinea pig small intestine. J Comp Neurol. 1995 May 22;356(1):101–114. doi: 10.1002/cne.903560107. [DOI] [PubMed] [Google Scholar]