PMID- 1964841
OWN - NLM
STAT- MEDLINE
DCOM- 19910523
LR  - 20190613
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 537
IP  - 1-2
DP  - 1990 Dec 24
TI  - Selective cross-activation/inhibition of second messenger systems and the 
      reduction of age-related deficits in the muscarinic control of dopamine release 
      from perifused rat striata.
PG  - 40-8
AB  - Possible alterations in muscarinic cholinergic (mACh) signal transduction in 
      senescence were studied in rat neostriata. Acetylcholine (ACh) activation of 
      striatal muscarinic heteroreceptors by carbachol or oxotremorine enhances 
      K(+)-evoked release of dopamine from perifused striata of 6- but not 24-month-old 
      rats. Present experiments determined the effects of simultaneous activation or 
      activation/inhibition of more than one second messenger on K(+)-evoked release of 
      DA from perifused striatal slices from these age groups. Combinations of 
      carbachol (500 microns), which stimulates inositol-1,4,5-bisphosphate (IP3) 
      production and inhibits cyclic AMP production, with oxotremorine (500 microns), 
      which inhibits cyclic AMP production, in the presence of 30 mM KCl (in a modified 
      Krebs-Ringer medium) reduced the age-related reduction in mAChR enhancement of DA 
      release (analyzed by HPLC coupled to electrochemical detection; 5 min fractions 
      were collected on ice in perchloric acid; flow rate 120 microliters/min). 
      Combinations of these agonists with the putative second messenger arachidonic 
      acid (10 microM), also enhanced K(+)-evoked release of DA in the striatal tissue 
      from the 24-month group. IP3 activation was lower in the striatal tissue from old 
      animals than those from young under all conditions, but 
      cross-activation/inhibition actually may have lowered the IP3 threshold necessary 
      for enhanced DA release to occur. In a subsequent experiment, pre-loading 
      striatal tissue from young animals with either carbachol or oxotremorine under 
      basal release conditions reduced the responding when the basal release medium was 
      switched to one containing 30 mM KCl and combinations of the agonists.(ABSTRACT 
      TRUNCATED AT 250 WORDS)
FAU - Joseph, J A
AU  - Joseph JA
AD  - Molecular Physiology and Genetics Section, Gerontology Research Center/NIA, 
      Francis Scott Key Medical Center, Baltimore, MD 21224.
FAU - Kowatch, M A
AU  - Kowatch MA
FAU - Maki, T
AU  - Maki T
FAU - Roth, G S
AU  - Roth GS
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Arachidonic Acids)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Receptors, Muscarinic)
RN  - 132-06-9 (Inosine Triphosphate)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 5RY0UWH1JL (Oxotremorine)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - I16QD7X297 (Neomycin)
RN  - RWP5GA015D (Potassium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Arachidonic Acid
MH  - Arachidonic Acids/metabolism
MH  - Biotransformation/drug effects
MH  - Carbachol/pharmacology
MH  - Corpus Striatum/*metabolism
MH  - Dopamine/*metabolism
MH  - In Vitro Techniques
MH  - Inosine Triphosphate/metabolism
MH  - Male
MH  - Neomycin/pharmacology
MH  - Oxotremorine/pharmacology
MH  - Perfusion
MH  - Phosphatidylinositol 4,5-Diphosphate
MH  - Phosphatidylinositols/metabolism
MH  - Potassium/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Muscarinic/*physiology
MH  - Second Messenger Systems/*physiology
MH  - Type C Phospholipases/physiology
EDAT- 1990/12/24 00:00
MHDA- 1990/12/24 00:01
CRDT- 1990/12/24 00:00
PHST- 1990/12/24 00:00 [pubmed]
PHST- 1990/12/24 00:01 [medline]
PHST- 1990/12/24 00:00 [entrez]
AID - 0006-8993(90)90337-B [pii]
AID - 10.1016/0006-8993(90)90337-b [doi]
PST - ppublish
SO  - Brain Res. 1990 Dec 24;537(1-2):40-8. doi: 10.1016/0006-8993(90)90337-b.