Streptozotocin-diabetes attenuates alpha 2-adrenoceptor agonist-induced delay in small intestinal transit in mice.
1. The effect of alpha 2-adrenoceptor agonists on gastrointestinal motility was assessed in normoglycaemic and streptozotocin-diabetic mice. 2. The alpha 2-adrenoceptor agonists used were: clonidine (0.1, 0.3 and 1 mg kg-1, azepexole (10, 20 and 40 mg kg-1), tizanidine (1, 3 and 10 mg kg-1) and ST-91 (10, 20 and 30 mg kg-1). 3. Acute hyperglycaemia was induced by D-(+)-glucose (5 g kg-1) and chronic hyperglycaemia by streptozotocin (200 mg kg-1) injection. 4. The gut motility was quantitated using the charcoal meal test. 5. The results indicate that in normoglycaemic and acutely hyperglycaemic mice, all of the alpha 2-adrenoceptor agonists used produced significant inhibition of meal transit. 6. However, in streptozotocin-diabetic mice, the anti-transit effect of alpha 2-adrenoceptor agonists was attenuated. 7. Since streptozotocin-induced diabetes but not acute hyperglycaemia was associated with the attenuation of anti-transit effect, elevated blood sugar is not the mechanism for the observed effect. 8. As with groups treated with clonidine, azepexole or tizanidine, the anti-transit effect of a peripherally acting alpha 2-adrenoceptor agonist, ST-91, was attenuated in streptozotocin-diabetic mice. This suggests the involvement of peripheral mechanism(s) in attenuating the anti-transit effect of alpha 2-adrenoceptor agonists. 9. These results identify the need for critical evaluation of the role and efficacy of alpha 2-adrenoceptor agonists in the therapeutic management of diabetic diarrhoea.
Ramabadran
K
K
Department of Anesthesiology, School of Medicine, New York University Medical Center, New York 10016.
Bansinath
M
M
Turndorf
H
H
Puig
M M
MM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology; D007421:Intestine, Small / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice
D000316:Adrenergic alpha-Agonists