Influences of hypothyroidism on lipid composition and inositol lipid-linked receptors responsiveness and protein kinase C (PKC) activity in the cerebral cortex of Lewis rats.
The influence of hypothyroidism (HO) induced by treatment with propylthiouracil on lipid composition, receptor responsiveness of M1-muscarinic receptors (M1AChRs) and metabotropic glutamate receptors (mGluRs) as well as on protein kinase C (PKC) activity was investigated in the cerebral cortex of Lewis rats. HO did not influence the lipid composition. There was a significant 2-fold increase of efficacy and 6-fold decrease of potency of carbachol-induced inositol phosphate (IP) accumulation in HO, with respect to control rats. The efficacy of trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD)-induced IP accumulation was also higher in HO (by 50%), without differences in EC50 values. The activities of soluble calcium-dependent and calcium-independent PKC were higher in HO than in control rats (both roughly 30%); membrane-associated PKCs were not modified. The data indicate that HO induces an increased responsiveness of M1AChRs and mGluRs and a rise in the soluble PKC activity that could be available and ready for translocation.
Pintor
A
A
Istituto Superiore di Sanità, Department of Pharmacology, Roma, Italy.
Fortuna
S
S
Lorenzini
P
P
Pascale
A
A
Battaini
F
F
Avellino
C
C
Malvezzi Campeggi
L
L
Salvati
S
S
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007037:Hypothyroidism / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D010890:Pirenzepine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*
D007295:Inositol Phosphates; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D010890:Pirenzepine; D007294:Inositol; D002217:Carbachol; D011493:Protein Kinase C