PMID- 16463401
OWN - NLM
STAT- MEDLINE
DCOM- 20060628
LR  - 20151119
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 59
IP  - 6
DP  - 2006 May
TI  - In vitro regulation of serotonin transporter activity by protein kinase A and 
      nicotinic acetylcholine receptors in the prefrontal cortex of rats.
PG  - 342-9
AB  - We investigated the effect of in vitro exposure to nicotinic acetylcholine 
      receptors (nAChRs), agonists, antagonists, and protein kinase A (PKA) modulators 
      on the activity of the serotonin transporter (SERT) in prefrontocortical (PFC) 
      synaptosomes. The plasma membrane SERT is an active transport mechanism specific 
      for serotonin. Receptors and second messengers capable of altering transporter 
      activity would be expected to have profound effects on serotonergic 
      neurotransmission and on functions involving serotonergic input, such as 
      cognition, anxiety, and mood. Our data suggest that activation of nAChRs, quite 
      likely via PKA, increase the activity of the SERT in the PFC and, thereby, can 
      alter 5-HT levels in a region important in the behavioral effects of nicotine and 
      5-HT. Nicotine at 4 microM increased [(3)H]5-HT uptake by 75%. Because the nAChR 
      antagonists mecamylamine and dihydro-beta-erythrodine (DHbetaE) both decreased 
      [(3)H]5-HT uptake into synaptosomes, it appeared that the SERT might be tonically 
      activated by acetylcholine present within our synaptosomal preparations. Blocking 
      PKA significantly decreased [(3)H]5-HT, while stimulation of PKA activity 
      significantly increased the uptake. A 66% decrease compared with control was 
      produced by 100 microM Rp-cAMP, and a 41% increase in 5-HT uptake over control 
      was observed with 30 microM Sp-cAMPs. Furthermore, the enhancement in uptake 
      produced by 4 microM nicotine was inhibited in a time-dependent fashion by 
      preincubation with 10 microM Rp-cAMP. A better understanding of the influence of 
      the cholinergic system and the receptors involved in the trafficking of SERT 
      would help clarify the important relationship between the cholinergic and 
      serotonergic systems and the role these systems play in behavior.
FAU - Awtry, Tammy L
AU  - Awtry TL
AD  - Department of Pharmacology and Physiology, The George Washington University 
      Medical Center, Washington, DC 20037, USA.
FAU - Frank, Julie G
AU  - Frank JG
FAU - Werling, Linda L
AU  - Werling LL
LA  - eng
GR  - DA14140/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Cholinergic Agonists)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Thionucleotides)
RN  - 10028-17-8 (Tritium)
RN  - 23255-54-1 (Dihydro-beta-Erythroidine)
RN  - 23645-17-2 (adenosine-3',5'-cyclic phosphorothioate)
RN  - 333DO1RDJY (Serotonin)
RN  - 6EE945D3OK (Mecamylamine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 7C0697DR9I (Atropine)
RN  - 8Y164V895Y (Carbachol)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Atropine/pharmacology
MH  - Carbachol/pharmacology
MH  - Cholinergic Agonists/pharmacology
MH  - Cyclic AMP/analogs & derivatives/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/*physiology
MH  - Dihydro-beta-Erythroidine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - In Vitro Techniques
MH  - Mecamylamine/pharmacology
MH  - Muscarinic Antagonists/pharmacology
MH  - Nicotine/pharmacology
MH  - Nicotinic Agonists/pharmacology
MH  - Nicotinic Antagonists/pharmacology
MH  - Prefrontal Cortex/cytology/drug effects/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Rats
MH  - Receptors, Nicotinic/*physiology
MH  - Serotonin/metabolism/pharmacokinetics
MH  - Serotonin Plasma Membrane Transport Proteins/*metabolism
MH  - Synaptosomes/drug effects
MH  - Thionucleotides/pharmacology
MH  - Time Factors
MH  - Tritium/pharmacokinetics
EDAT- 2006/02/08 09:00
MHDA- 2006/06/29 09:00
CRDT- 2006/02/08 09:00
PHST- 2006/02/08 09:00 [pubmed]
PHST- 2006/06/29 09:00 [medline]
PHST- 2006/02/08 09:00 [entrez]
AID - 10.1002/syn.20251 [doi]
PST - ppublish
SO  - Synapse. 2006 May;59(6):342-9. doi: 10.1002/syn.20251.