QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.059204v1 309/1/310    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, H.-Z. Articles by Wood, J. D. Search for Related Content PubMed PubMed Citation Articles by Hu, H.-Z. Articles by Wood, J. D.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Metabotropic Signal Transduction for Bradykinin in Submucosal Neurons of Guinea Pig Small Intestine

Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio

Intracellular recording methods with "sharp" microelectrodes were used to study signal transduction mechanisms underlying the excitatory action of bradykinin (BK) in morphologically identified neurons in the small intestinal submucosal plexus. Exposure to BK evoked slowly activating membrane depolarization and enhanced excitability associated with increased input resistance in AH-type and decreased input resistance in S-type neurons. Preincubation with pertussis toxin did not affect the BK-evoked responses. Pretreatment with the cyclooxygenase inhibitors indomethacin or piroxicam suppressed or abolished the BK-evoked responses. Application of prostaglandin (PG) E₂ or PG analogs evoked BK-like depolarizing responses in the submucosal plexus with a potency order of PGE₂ > PGE₁ > 17-phenyl trinor-PGE₂ > PGI₂ > sulprostone > PGF₂. Depolarizing responses to bradykinin or PGE₂ in S-type neurons were suppressed in the presence of the phospholipase C inhibitor U73122 [(1-6-[([17]-3-methoxyestra-1,3,5[10]-tren-17-71)amino]hexyl)-1H-pyrrole-2,5-dione)], but not the inactive analog U73343 [(1-6-[([17]-3-methoxyestra-1,3,5[10]trien-17yl)amino]hexyl)-2,5-pyrrolidinedione)]. The inositol-1,4,5-trisphosphate receptor antagonist 2-aminoethoxy-diphenylborane and the calmodulin inhibitor W-7, but not ryanodine, suppressed both bradykinin- and PGE₂-evoked responses. KN-62, an inhibitor of calmodulin kinases, or GF109203X, a specific protein kinase C inhibitor, suppressed both BK- and PGE₂-evoked depolarizing responses. Selective protein kinase A inhibitors did not alter BK- or PGE₂-evoked depolarizing responses in S neurons. The results suggest that BK stimulates synthesis and release of PGE₂, which acts at EP₁ receptors to evoke depolarizing responses in submucosal neurons. The postreceptor transduction cascade includes activation of phospholipase C, inositol-1,4,5-trisphosphate production, intraneuronal Ca²⁺ mobilization, activation of protein kinase C and/or calmodulin kinases, and phosphorylation of cationic channels.

Address correspondence to: Dr. Jackie D. Wood, Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210-1218. E-mail: wood.13{at}osu.edu

This article has been cited by other articles:

				N. Gao, H.-Z. Hu, S. Liu, C. Gao, Y. Xia, and J. D. Wood Stimulation of adenosine A1 and A2A receptors by AMP in the submucosal plexus of guinea pig small intestine Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G492 - G500. [Abstract] [Full Text] [PDF]