Influence of spaceflight, hindlimb suspension, and venous occlusion on alpha 1-adrenoceptors in rat vena cava.
Effects of hindlimb suspension, spaceflight, and venous occlusion were examined in isolated strips from rat vena cava by using both [3H]prazosin-binding and contraction responses evoked by norepinephrine. Sensitivity to norepinephrine was decreased without modification of the maximal contractile response. Furthermore, the high K(+)-induced contractions were not affected, suggesting that there was no interference with voltage-dependent Ca2+ channels. The sensitivity of the norepinephrine-induced contraction to prazosin was decreased, and Scatchard analysis of [3H]prazosin binding indicated an increase in the dissociation constant without variation in maximal binding capacity. A similar increase in the dissociation constant was obtained in control rats after pretreatment with 3 microM norepinephrine or 0.1 microM phorbol 12,13-dibutyrate to desensitize the protein kinase C. This effect was completely abolished in the presence of GF-109203X, a selective inhibitor of protein kinase C. Taken together, these data indicate that altered gravity conditions induce a desensitization of alpha 1B-adrenoceptors depending on increased protein kinase C activity. This effect can be mimicked by venous occlusion and may be responsible for reduced contractile responses to norepinephrine.
Sayet
I
I
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, Centre National de la Recherche Scientifique 1489, Université de Bordeaux II, France.
Neuilly
G
G
Mironneau
J
J
Mironneau
C
C
D000818:Animals; D006614:Hindlimb / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011224:Prazosin / Q000493:pharmacokinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D013026:Space Flight; D014684:Venae Cavae / Q000378:metabolism / Q000502:physiology*; D018474:Weightlessness Simulation
D007211:Indoles; D008301:Maleimides; D018340:Receptors, Adrenergic, alpha-1; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D009638:Norepinephrine; D011224:Prazosin