{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:21:36Z","timestamp":1791336096497,"version":"4.3.1"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:p>Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the particulate guanylyl cyclase and the nitric oxide donor S-nitroso-n-acetylpenicillamine (SNAP) was used to activate the soluble guanylyl cyclase. CNG channel activity was monitored by measuring Ca2+ or Mn2+ influx through the channels using the fluorescent dye, fura-2. We found that in HEK-NPRA cells, ANP-induced increases in cGMP levels activated CNG channels in a dose-dependent manner (0.05\u201310 nM), whereas SNAP (0.01\u2013100 \u03bcM) induced increases in cGMP levels triggered little or no activation of CNG channels (P &amp;lt; 0.01). After pretreatment with 100 \u03bcM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, ANP-induced Mn2+ influx through CNG channels was significantly enhanced, while SNAP-induced Mn2+ influx remained small. In contrast, we found that in the presence of IBMX, both 1 nM ANP and 100 \u03bcM SNAP triggered similar increases in total cGMP levels. We next sought to determine if cGMP signals are compartmentalized in VSMCs, which endogenously express particulate and soluble guanylyl cyclase. We found that 10 nM ANP induced activation of CNG channels more readily than 100 \u03bcM SNAP; whereas 100 \u03bcM SNAP triggered higher levels of total cellular cGMP accumulation. These results suggest that cGMP signals are spatially segregated within cells, and that the functional compartmentalization of cGMP signals may underlie the unique actions of ANP and nitric oxide.<\/jats:p>","DOI":"10.1085\/jgp.200509403","type":"journal-article","created":{"date-parts":[[2006,6,13]],"date-time":"2006-06-13T00:54:09Z","timestamp":1150160049000},"page":"3-14","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":95,"title":["Natriuretic Peptides and Nitric Oxide Stimulate cGMP Synthesis in Different Cellular Compartments"],"prefix":"10.1085","volume":"128","author":[{"given":"Leslie A.","family":"Piggott","sequence":"first","affiliation":[{"name":"1Program in Cell and Regulatory Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77225"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Hassell","sequence":"additional","affiliation":[{"name":"3Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Berkova","sequence":"additional","affiliation":[{"name":"3Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Morris","sequence":"additional","affiliation":[{"name":"1Program in Cell and Regulatory Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77225"},{"name":"3Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Silberbach","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics and the Heart Research Center, Oregon Health and Science University, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Rich","sequence":"additional","affiliation":[{"name":"1Program in Cell and Regulatory Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77225"},{"name":"3Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,6,12]]},"reference":[{"key":"2023072618305404700_BIB1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1113\/jphysiol.2001.012929","volume":"540","year":"2002","journal-title":"J. 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