Effects of pertussis toxin on the alpha 2-adrenoceptor-inhibitory GTP-binding protein-adenylate cyclase system in rat brain: pharmacological and neurochemical studies.
Behavioral excitement and the increase in locomotion were observed in male adult rats four days after an intraventricular injection of 5 micrograms pertussis toxin (IAP). Clonidine (100 micrograms/kg s.c.)-induced locomotor hypoactivity was not observed in animals pretreated with 1 and 5 micrograms IAP. IAP caused a significant (P less than 0.05) decrease in the KD value of [3H]clonidine binding and enhanced GTP (1 microM)-induced decrease in the binding to cortical membranes from rat brain. In addition, the inhibition of adenylate cyclase induced by alpha 2-receptor stimulation (100 microM adrenaline plus 100 microM propranolol) was completely suppressed in the cerebral cortical membranes by IAP pretreatment. It is suggested that the system consisting of alpha 2-receptor, the inhibitory GTP-binding protein (Ni) and adenylate cyclase inhibits some animal behaviors and cyclic AMP formation. Moreover, IAP seems to inactivate Ni, subsequently producing behavioral excitement and it inhibits clonidine-induced sedation.
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003000:Clonidine / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003000:Clonidine; D004837:Epinephrine