Acute and chronic studies on functional aspects of coexistence.
Autoinhibition of acetylcholine release by the coexisting peptide galanin in the septal afferents to the hippocampus of the rat was examined in tissue slices from the hippocampus. Galanin inhibits the evoked release of the coexisting neurotransmitter, acetylcholine, in the ventral hippocampus, providing an example of autoinhibition of release of a neurotransmitter by one of the coexisting neurotransmitters. The galanin mediated inhibition of the acetylcholine release is a complement to the well known strong cholinergic autoinhibition. The effects of the coexisting galanin and acetylcholine on several second messenger systems were also examined: acetylcholine acting at muscarinic receptors depresses cyclic adenosine 3',5'-monophosphate and stimulates elevation of cyclic guanosine 3',5'-monophosphate levels, whereas neither cyclic adenosine 3',5'-monophosphate nor cyclic guanosine 3',5'-monophosphate levels were affected by galanin (1 microM). Galanin however inhibited partly the muscarinic stimulation of phosphoinositide breakdown, suggesting that inositol phosphate(s) or diacylglycerol may act as second messenger(s) of the galanin action in the hippocampus. The effects of chronic changes in firing rate on the coexisting neurotransmitters in the rat ventral spinal cord containing serotonin, thyrotropin releasing hormone, substance P and substance K were examined. The tissue levels of the coexisting transmitters were studied in rats chronically treated with imipramine (14 days; 2 x 10 mumoles/kg/day) and zimelidine (14 days; 2 x 10 mumoles/kg/day). Upon treatment with zimelidine the tissue levels of the serotonin metabolite 5-hydroxyindoleacetic acid fall by 32% while thyrotropin releasing hormone levels seem to increase 35% and substance P/substance K levels also increase 48 and 72% respectively. Imipramine treatment resulted in similar although less pronounced changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Bartfai
T
T
Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Bertorelli
R
R
Consolo
S
S
Diaz-Arnesto
L
L
Fisone
G
G
Hökfelt
T
T
Iverfeldt
K
K
Palazzi
E
E
Ogren
S O
SO
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D019004:Galanin; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D015288:Neurokinin A / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D013373:Substance P / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology; D015031:Zimeldine / Q000494:pharmacology
D010455:Peptides; D012701:Serotonin; D013373:Substance P; D015031:Zimeldine; D013973:Thyrotropin-Releasing Hormone; D015288:Neurokinin A; D019004:Galanin; D000109:Acetylcholine; D007099:Imipramine