title: Reduced sciatic nerve substance P and calcitonin gene-related peptide in rats with short-term diabetes or central hypoxaemia co-exist with normal messenger RNA levels in the lumbar dorsal root ganglia.
abstract: Endoneurial hypoxia of ischaemic origin is believed to cause the reduction in sciatic nerve substance P levels in experimentally diabetic rats. The first part of this study was designed to determine whether the changes seen extended to another neuropeptide, calcitonin gene-related peptide, and to reveal any correlation between substance P and calcitonin gene-related peptide levels in the sciatic nerve of both diabetic and centrally hypoxaemic rats. Comparison of streptozotocin diabetic rats (four-week duration) with their control group showed clear reductions in both substance P-like immunoreactivity (control = 225 +/- 20 pg/mg protein, diabetic = 139 +/- 19; P < 0.01) and calcitonin gene-related peptide-like immunoreactivity (control = 9.08 +/- 0.65 ng/mg protein, diabetic = 4.43 +/- 0.44; P < 0.001). A similar pattern was seen with the comparison of five-week centrally hypoxaemic rats (housed in 10% O2) with their controls for both substance P-like immunoreactivity (control = 222 +/- 10 pg/mg protein, hypoxic = 148 +/- 13; P < 0.001) and calcitonin gene-related peptide-like immunoreactivity (control = 6.58 +/- 0.42 ng/mg protein, hypoxic = 3.01 +/- 0.45; P < 0.001). Calcitonin gene-related peptide levels correlated closely with substance P levels in both the diabetes and central hypoxaemia studies (r2 = 0.69 and 0.62, respectively). The second part of this study measured the messenger RNA levels of the substance P precursor, preprotachykinin-A, and calcitonin gene-related peptide messenger RNA in the L4 and L5 dorsal root ganglia of control, diabetic and centrally hypoxaemic rats. There was no change in preprotachykinin-A or calcitonin gene-related peptide messenger RNA levels between any of the groups, suggesting that the sciatic nerve decreases in substance P and calcitonin gene-related peptide described above are post-transcriptional in origin.
authors.affiliation: Department of Pharmacology, Queen Mary and Westfield College, London, U.K.
authors.forename: W J
authors.initials: WJ
authors.lastname: Brewster
authors.forename: L T
authors.initials: LT
authors.lastname: Diemel
authors.forename: R M
authors.initials: RM
authors.lastname: Leach
authors.forename: D R
authors.initials: DR
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism*; D013373:Substance P / Q000096:biosynthesis* / Q000276:immunology; D015320:Tachykinins / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide