title: Role of alpha2-adrenoceptors on the hyperglycaemic and insulin secretory effects derived from alpha1- and beta-adrenoceptor stimulation in the rabbit.
abstract: 1. In conscious fasted rabbits the insulin secretory response induced by the intravenous infusion of the alpha1-adrenoceptor agonist, amidephrine (10 microg kg(-1) min(-1)) was blocked by the simultaneous administration of clonidine (2 microg kg(-1) min(-1) i.v.). 2. The excitatory effect of amidephrine (10 microg kg(-1) min(-1)) on insulin secretion was similarly suppressed by the concomitant infusion of the selective alpha2-adrenoceptor agonist UK14304 (1 microg kg(-1) min(-1)). Both, the increase in blood glucose and the inhibition of insulin secretion found with UK14304 when infused alone were antagonized in rabbits previously treated with the very selective alpha2-adrenoceptor antagonist 2-methoxyidazoxan (1.5 microg kg(-1) min(-1)). 3. The combined administration of amidephrine (3 microg kg(-1) min(-1)) and isoprenaline (0.3 microg kg(-1) min(-1)) evoked a potentiated increase in insulin plasma levels in the face of a weak hyperglycaemia, an established reduction in blood pressure and tachycardia. 4. The potentiated insulin secretory response derived from alpha1- and beta-adrenoceptor stimulation was blunted by clonidine administration. In its presence a sustained hyperglycaemic response was found. 5. The increase in plasma lactate levels resulting from dual adrenoceptor stimulation (amidephrine: 10 microg kg(-1) min(-1) + salbutamol: 0.3 microg kg(-1) min(-1)) was smaller than the expected should addition or potentiation occurred. 6. Our results point to a possible physiological role played by alpha2-adrenoceptors on insulin secretion, since their stimulation by the endogenous catecholamines could lead to inhibition of insulin release, masking any potentiated response that otherwise should have appeared from alpha1- and beta-adrenoceptor stimulation.
authors.affiliation: Departamento de Fisiologia y Farmacologia, Facultad de Medicina, Universidad de Salamanca, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Barrado
authors.forename: C
authors.initials: C
authors.lastname: Sancho
authors.forename: J
authors.initials: J
authors.lastname: Palomero
authors.forename: J
authors.initials: J
authors.lastname: Moratinos
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D019344:Lactic Acid / Q000097:blood; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D004983:Ethanolamines; D007328:Insulin; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D019344:Lactic Acid; D000068438:Brimonidine Tartrate; C016980:amidephrine; D003000:Clonidine; D000420:Albuterol