Chronic bombesin treatment increased the [3H]spiperone binding, glutamate decarboxylase and choline acetyltransferase activity in the rat brain.
The effects of chronic bombesin (BBS) on [3H]spiperone (SPD) binding activity, choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and glutamate decarboxylase (GAD) were investigated in the rat brain corpus striatum (CS). The chronic i.p. administration of BBS to rats increased: (1) the specific [3H]SPD binding to the striatal Pm (plasma membrane) (16%, P less than 0.03 and 34%, P less than 0.008 at 5 micrograms/kg respectively), (2) the specific GAD activity in the CS by 52% (5 micrograms/kg, n.s.) and 46% (10 micrograms/kg, P less than 0.05) respectively, (3) the specific ChAT activity in the CS by 54% (10 micrograms/kg, P less than 0.002), and (4) the specific AChE activity by 23% (10 micrograms/kg, P less than 0.02) after 14 days. It increased only: (1) the specific [3H]SPD binding by 29% (P less than 0.001, at 10 micrograms/kg) and (2) the specific GAD activity by 23% (P less than 0.015, 10 micrograms/kg), after 7 days. Neither ChAT nor AChE activity was affected after 7 days treatment of BBS at 10 micrograms/kg. In vitro study showed that BBS at 0.2 microM did not affect any of the neurochemical parameters examined in the CS. Thus, the changes in brain chemistry caused by chronic BBS were not due to direct effects of BBS but may be mediated through its metabolites or CCK release. Data indicate that the central effects of peripherally administered BBS are dependent on both the duration and the dosage of the drug treatment and that the dopaminergic and GABAergic systems seem to be more vulnerable to chronic BBS than the cholinergic system in the rat brain CS.(ABSTRACT TRUNCATED AT 250 WORDS)
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D013134:Spiperone; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; D001839:Bombesin