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Expression Level of Canonical Transient Receptor Potential (TRPC) Channels is Increased in the Adrenal Medulla of Ossabaw Miniature Pigs Manifesting the Metabolic Syndrome
Author(s) -
Hu Guoqing,
Neeb Zachary P,
Sturek Michael,
Obukhov Alexander G
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1201.14
Subject(s) - trpc , trpc5 , endocrinology , medicine , transient receptor potential channel , trpc3 , trpc1 , chemistry , trpc6 , receptor , angiotensin ii , biology
The objective of this study was to investigate whether pig adrenal chromaffin cells (ACC) express G q/11‐protein coupled receptors (GPCR) and whether excess kcal atherogenic diet that elicits metabolic syndrome (MetS) in Ossabaw pigs increases TRPC expression in the adrenal medulla (AM). TRPCs are Ca 2+ ‐permeable cation channels that are activated by agonists of GPCR. TRPC channels mediate circulating hormone‐stimulated, voltage‐independent exocytosis of catecholamines from ACC. Higher levels of plasma epinephrine are found in MetS animals vs. lean control animals, suggesting enhanced exocytosis from AM. We used molecular biological, biochemical and fluorescence imaging methods to study GPCRs and TRPCs in ACC isolated from AM of the lean and MetS pigs. Using fluorescence imaging, we demonstrated that angiotensin II, muscarinic, and histamine GPCRs are expressed in porcine ACC, and that the receptors’ activation stimulates Ca 2+ /Mn 2+ influx. We cloned pig TRPC1 and TRPC3–7 channels. We detected transcripts of TRPC1, TRPC5 and TRPC6 in the total RNA isolated from AM. The expression of TRPC1, TRPC5 and TRPC6 was significantly higher in AM from MetS vs. lean pigs. We conclude that an abnormal up‐regulation of adrenal TRPCs in MetS may underlie the elevated levels of plasma epinephrine. Support: NIH RR013223 and HL062552 to MS and HL083381 to AGO.