{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:58:09Z","timestamp":1778273889617,"version":"3.51.4"},"reference-count":53,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2002,6,1]]},"abstract":"<jats:p>Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a PGE<jats:sub>2<\/jats:sub>-mediated release of substance P (SP) from renal pelvic nerves. The role of cAMP activation in the PGE<jats:sub>2<\/jats:sub>-mediated release of SP was studied by examining the effects of the adenylyl cyclase (AC) activator forskolin and AC inhibitor dideoxyadenosine (DDA). Forskolin enhanced the bradykinin-mediated release of SP from an isolated rat renal pelvic wall preparation, from 7.3 \u00b1 1.3 to 15.6 \u00b1 3.0 pg\/min. PGE<jats:sub>2<\/jats:sub>at a subthreshold concentration for SP release mimicked the effects of forskolin. The EP<jats:sub>2<\/jats:sub>receptor agonist butaprost, 15 \u03bcM, and PGE<jats:sub>2<\/jats:sub>, 0.14 \u03bcM, produced similar increases in SP release, from 5.8 \u00b1 0.8 to 17.0 \u00b1 2.3 pg\/min and from 8.0 \u00b1 1.3 to 21.6 \u00b1 2.7 pg\/min. DDA blocked the SP release produced by butaprost and PGE<jats:sub>2<\/jats:sub>. The PGE<jats:sub>2<\/jats:sub>-induced release of SP was also blocked by the PKA inhibitors PKI<jats:sub>14\u201322<\/jats:sub>and H-89. Studies in anesthetized rats showed that renal pelvic administration of butaprost, 10 \u03bcM, and PGE<jats:sub>2<\/jats:sub>, 0.14 \u03bcM, resulted in similar ARNA responses, 1,520 \u00b1 390 and 1,170 \u00b1 270% \u00b7 s (area under the curve of ARNA vs. time) that were blocked by DDA. Likewise, the ARNA response to increased renal pelvic pressure, 7,180 \u00b1 710% \u00b7 s, was blocked by DDA. In conclusion, PGE<jats:sub>2<\/jats:sub>activates the cAMP-PKA pathway leading to a release of SP and activation of renal pelvic mechanosensory nerve fibers.<\/jats:p>","DOI":"10.1152\/ajpregu.00701.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:24:08Z","timestamp":1425414248000},"page":"R1618-R1627","source":"Crossref","is-referenced-by-count":40,"title":["PGE<sub>2<\/sub>increases release of substance P from renal sensory nerves by activating the cAMP-PKA transduction cascade"],"prefix":"10.1152","volume":"282","author":[{"given":"Ulla C.","family":"Kopp","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Department of Veterans Affairs Medical Center, Iowa City 52246; and University of Iowa College of Medicine, Iowa City, Iowa 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Z.","family":"Cicha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 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