Dopamine D1 receptors are involved in the ACTH-induced reversal of hemorrhagic shock.
In an experimental model of volume-controlled hemorrhagic shock causing the death of all rats within 30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropic hormone fragment 1-24 (ACTH-(1-24)) (160 micrograms/kg) induced a prompt and sustained improvement of cardiovascular and respiratory function, with 100% survival 2 h after treatment. Pretreatment with either haloperidol, 300 micrograms/kg i.v. (antagonist at dopamine D1 and D2 receptors), or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate (SCH 23390), 50 micrograms/kg intraperitoneally (selective antagonist at dopamine D1 receptors), significantly inhibited the effect of ACTH-(1-24). A complete inhibition was produced by intracerebroventricular pretreatment with SCH 23390 (0.1 micrograms/rat). On the other hand, both i.v. and i.c.v. pretreatment with l-sulpiride (selective antagonist at dopamine D2 receptors) (25 mg/kg and 80 micrograms/rat, respectively) had only minor effects. These data suggest that the mechanism of the ACTH-induced reversal of hemorrhagic shock involves the activation of dopamine D1 receptors in the brain.
Bazzani
C
C
Institute of Pharmacology, University of Modena, Italy.
Nardi
M G
MG
Ferrante
F
F
Bertolini
A
A
Guarini
S
S
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003366:Cosyntropin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology
D001552:Benzazepines; D010446:Peptide Fragments; D017447:Receptors, Dopamine D1; D003366:Cosyntropin; D013469:Sulpiride; D006220:Haloperidol