title: Effect of insulin and clonidine on the evoked release of norepinephrine and serotonin from the nucleus tractus solitarius of the diabetic rat.
abstract: Dorsal medullary brain slices containing primarily the nucleus tractus solitarius (NTS) were obtained from normal or 40- to 50-day streptozotocin-diabetic rats and employed for superfusion studies of evoked transmitter release. Electrically stimulated (25 mA, 2-ms pulses, 3 Hz, 1 min) release of [3H]norepinephrine ([3H]NE) or [3H]5-hydroxytryptamine ([3H]5-HT) from 400-microns NTS slices stimulated at 75 min (S1) and 130 min (S2) resulted in S2/S1 release ratios that were not different between normal controls or diabetic control groups. Perfusion of normal [3H]NE-loaded slices with 0.1 mumol/l clonidine reduced the S2/S1 ratio by 23% (p < 0.05) which was uniform in the caudal, subpostremal, and intermediate segment levels of the NTS. In diabetic NTS slices, the S2/S1 ratio was significantly less reduced by clonidine in both the subpostremal (-3%) and intermediate (-11%) slice regions. Blockade of alpha 2-adrenoceptors with yohimbine (0.1 mumol/l) enhanced (p < 0.05) [3H]NE release (S2/S1 ratios) in slices from both normal and diabetic rats. Perfusion of [3H]NE-loaded slices with 5 mU/ml insulin did not affect S2 release. Evoked S2/S1 release ratios from NTS slices loaded with [3H]5-HT did not differ between normal control and diabetic control groups. Clonidine (0.1 mumol/l) reduced S2-evoked release in both normal (-30%) and diabetic (-44%) slices, but the groups were not different from each other. Superfusion with 5 mU/ml insulin did not alter S2/S1 ratios in normal [3H]5-HT loaded slices, but did increase the diabetic NTS slice S2/S1 ratio to 1.40 +/- 0.06 (p < 0.01). In summary, it appears that alpha 2-adrenoceptor-mediated inhibition of [3H]NE release in the NTS was selectively attenuated in a regionally specific manner in diabetic animals. Release inhibition may be associated with receptor downregulation in NTS regions associated with cardiovascular reflex transmission. Insulin superfusion augmented [3H]5-HT release in the diabetic NTS slices, possibly through increased transmitter synthesis or improved synaptic release.
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Mich., USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Dunbar
authors.forename: C
authors.initials: C
authors.lastname: Clough-Helfman
authors.forename: R A
authors.initials: RA
authors.lastname: Barraco
authors.forename: G F
authors.initials: GF
authors.lastname: Anderson
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004558:Electric Stimulation; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000316:Adrenergic alpha-Agonists; D007328:Insulin; D012701:Serotonin; D013311:Streptozocin; D003000:Clonidine; D009638:Norepinephrine