Huiming Zhang and Jun-Ge Yu contributed equally to this work.
Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system
Article first published online: 14 SEP 2001
Copyright © 2001 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 439, Issue 1, pages 46–64, 8 October 2001
How to Cite
Christofi, F. L., Zhang, H., Yu, J.-G., Guzman, J., Xue, J., Kim, M., Wang, Y.-Z. and Cooke, H. J. (2001), Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system. J. Comp. Neurol., 439: 46–64. doi: 10.1002/cne.1334
- Issue published online: 14 SEP 2001
- Article first published online: 14 SEP 2001
- Manuscript Revised: 9 JUL 2001
- Manuscript Accepted: 9 JUL 2001
- Manuscript Received: 13 APR 2001
- NIH. Grant Numbers: R01 DK44179, NCRR 1S10 RR11434, R01 DK57016, DK44179-07S1
- Samuel J. Roessler Scholarship
- adenosine receptor immunoreactivity;
- enteric nervous system;
- vasoactive intestinal peptide;
- substance P;
- adenosine receptor colocalization;
- human intestine;
- A1, A2a, A2b, A3 receptors
Adenosine receptors (ADORs) in the enteric nervous system may be of importance in the control of motor and secretomotor functions. Gene expression and distribution of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was investigated using immunochemical, Western blotting, RT-PCR, and short-circuit current (Isc) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were differentially expressed in neural and nonneural layers of the jejunum, ileum, colon, and cecum and in HT-29, T-84, T98G, and Bon cell lines. A1R, A2aR, A2bR, and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5-immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR occurs in 57% of substance P-positive jejunal submucosal neurons (putative intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are coexpressed in enteric neurons and epithelial cells. 5′-N-methylcarboxamidoadenosine or carbachol evoked an increase in Isc. A2bR IR is more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional differences also exist in smooth muscle expression of ADOR IR(s). It is concluded that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the regulation of neural reflexes in the human gut. Clear cell and regional differences exist in ADOR gene expression, distribution, localization, and coexpression. J. Comp. Neurol. 439:46–64, 2001. © 2001 Wiley-Liss, Inc.