Effect of insulin and clonidine on the evoked release of norepinephrine and serotonin from the nucleus tractus solitarius of the diabetic rat.
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.
Dunbar
J C
JC
Department of Physiology, Wayne State University, Detroit, Mich., USA.
Clough-Helfman
C
C
Barraco
R A
RA
Anderson
G F
GF
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
D000316:Adrenergic alpha-Agonists; D007328:Insulin; D012701:Serotonin; D013311:Streptozocin; D003000:Clonidine; D009638:Norepinephrine