Alpha- and beta-adrenoceptor cross-talk in the regulation of glycogenolysis in dog and guinea-pig liver.
The dog liver glycogenolytic response to isoprenaline (EC50 = 3 x 10(-9) M) was selectively blocked by 10(-5) M of practolol, but not by butoxamine. In contrast, the glycogenolytic response to isoprenaline (EC50 = 3 x 10(-7) M) was inhibited by 10(-6) M of butoxamine, but not by practolol, in the guinea-pig liver. This suggests that, in the dog, the isoprenaline response is dominated by beta 1-adrenoceptors, while in the guinea-pig beta 2-receptors control such response. Glucose release from dog and guinea-pig liver slices was also stimulated by amidephrine (EC50 = 10(-6) M in the dog and 4 x 10(-5) M in the guinea-pig). Both prazosin and yohimbine blocked this response. The effectiveness of clonidine as a glucose-mobilizing agent could only be established in the dog liver. Prazosin showed greater activity than yohimbine in antagonizing the response to both agonists. In the dog, low concentrations of alpha-adrenoceptor agonists (10(-9) M), that failed to modify the basal glucose release per se, selectively depressed the isoprenaline response. Prazosin, but not yohimbine, reversed this inhibitory effect. It is concluded that glucose release from the dog liver is regulated by two opposite mechanisms that seem to be associated to alpha 1-adrenoceptors (inhibitory) and to beta 1-adrenoceptors (stimulatory).
Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
R
R
Maroto
S
S
Calvo
C
C
Sancho
E
E
Esquerro
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D004983:Ethanolamines; D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C016980:amidephrine; D005947:Glucose; D007545:Isoproterenol; D003000:Clonidine; D000420:Albuterol