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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.
AuthorsM J García-Barrado, C Sancho, J Palomero, J Moratinos
JournalJournal of autonomic pharmacology (J Auton Pharmacol) Vol. 18 Issue 5 Pg. 287-95 (Oct 1998) ISSN: 0144-1795 [Print] England
PMID9831229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-Agonists
  • Blood Glucose
  • Ethanolamines
  • Insulin
  • Quinoxalines
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, Adrenergic, beta
  • Lactic Acid
  • Brimonidine Tartrate
  • amidephrine
  • Clonidine
  • Albuterol
Topics
  • Adrenergic alpha-Agonists (pharmacology)
  • Albuterol (pharmacology)
  • Animals
  • Blood Glucose (analysis)
  • Blood Pressure (drug effects)
  • Brimonidine Tartrate
  • Clonidine (pharmacology)
  • Ethanolamines (pharmacology)
  • Heart Rate (drug effects)
  • Hyperglycemia (physiopathology)
  • Insulin (metabolism)
  • Insulin Secretion
  • Lactic Acid (blood)
  • Male
  • Quinoxalines (pharmacology)
  • Rabbits
  • Receptors, Adrenergic, alpha-1 (physiology)
  • Receptors, Adrenergic, alpha-2 (physiology)
  • Receptors, Adrenergic, beta (physiology)

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