Differences between rat dorsal and ventral hippocampus in muscarinic receptor agonist binding and interaction with phospholipase C.
Carbachol, a full muscarinic receptor agonist, stimulated [3H]inositol phosphate accumulation in both the ventral and dorsal hippocampus, but its efficacy and affinity were higher in the former area. The partial agonist oxotremorine had a weak stimulatory effect in both regions. The affinity profiles of pirenzepine and AF-DX 116 in antagonizing carbachol-stimulated [3H]inositol phosphate accumulation indicated that M1 and M3 receptors contributed equally to the response in either region. On the other hand, there were no differences in the receptor density, or in the distribution of muscarinic receptor subtypes between the two regions of the hippocampus which could account for the effect as determined in binding experiments with selective antagonists. Analysis of carbachol binding curves did, instead, indicate a difference in the way the agonist interacted with the receptors within the hippocampus, i.e., carbachol recognized three agonist affinity states (superhigh, high and low) in the ventral hippocampus, and only two (high and low) in the dorsal part. The findings thus suggested that the regional diversity in the efficacy of carbachol in stimulating phosphoinositide turnover was related to the complexity with which it bound to muscarinic receptors. Transduction processes that intervene between changes in the muscarinic receptors' conformation and activation of phospholipase C might be relevant to these differences.
Garcia Ruiz
A J
AJ
Laboratory of Cholinergic Neuropharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Zambelli
M
M
La Porta
C
C
Ladinsky
H
H
Consolo
S
S
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005663:Furans; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D019832:N-Methylscopolamine; D009281:Naphthalenes; D010095:Oxotremorine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010880:Piperidines; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D000470:Alkaloids; D005663:Furans; D009281:Naphthalenes; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D010880:Piperidines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D006165:Guanylyl Imidodiphosphate; D010890:Pirenzepine; D010095:Oxotremorine; D002217:Carbachol; D010738:Type C Phospholipases; C048172:himbacine; C048593:otenzepad; D019832:N-Methylscopolamine