PMID- 2901110
OWN - NLM
STAT- MEDLINE
DCOM- 19880929
LR  - 20181212
IS  - 0950-1193 (Print)
IS  - 0950-1193 (Linking)
VI  - 234
IP  - 1274
DP  - 1988 Jun 22
TI  - Mechanism of synaptic inhibition by noradrenaline acting at alpha 
      2-adrenoceptors.
PG  - 85-114
AB  - The actions of agonists at alpha 2-adrenoceptors were investigated on single 
      cells of the submucous plexus of the guinea pig small intestine. Intracellular 
      recordings were made from neurons in vitro, and noradrenaline and other agonists 
      were applied by adding them to the superfusion solution. The actions of 
      noradrenaline released from terminals of sympathetic nerves was also studied by 
      stimulating the nerves and recording the inhibitory postsynaptic current; this 
      current can be mimicked by brief applications of noradrenaline from a pipette tip 
      positioned within 50 micron of the neuron. The alpha 2-adrenoceptor-bound 
      noradrenaline with an apparent dissociation constant of 15 microM, determined by 
      the method of partial irreversible receptor inactivation: clonidine and 
      5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) had dissociation 
      constants of 36 nM and 2.5 microM respectively. Noradrenaline and UK 14304 caused 
      maximal hyperpolarizations, or outward currents; clonidine was a full agonist in 
      only 4 of 35 cells, a partial agonist in 25 cells, and without effect in 4 cells. 
      Clonidine acted as a competitive antagonist of noradrenaline in those cells in 
      which it lacked agonist action; its dissociation equilibrium constant determined 
      by Schild analysis was about 20 nM. The potassium conductance increased by the 
      alpha 2-adrenoceptor agonists, whether they were applied exogenously or released 
      by stimulation of presynaptic nerves, showed marked inward rectification. The 
      neurons showed inward rectification also in the absence of agonist; both types of 
      rectification were eliminated by rubidium (2 mM), barium (3-30 microM) and 
      caesium (2 mM). When the recording electrodes contained the nonhydrolysable 
      derivative of guanosine 5'-triphosphate (GTP), guanosine 
      5'-O-(3-thiotriphosphate, GTP-gamma-S), the effects of applied alpha 
      2-adrenoceptor agonists did not reverse when they were washed from the tissue, 
      implying that GTP hydrolysis is necessary for the termination of agonist action. 
      Pretreatment with pertussis toxin abolished the inhibitory synaptic potential 
      (IPSP) and agonist-induced hyperpolarizations. Phorbol 12,13-dibutyrate, 
      forskolin, cholera toxin and sodium fluoride did not affect the responses to 
      alpha 2-adrenoceptor agonists. The synaptic hyperpolarization resulting from 
      sympathetic nerve stimulation, or the hyperpolarization evoked by a brief (3-5 
      ms) application of noradrenaline, began after a latency of about 30 and 60 ms 
      respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Surprenant, A
AU  - Surprenant A
AD  - Vollum Institute, Oregon Health Sciences University, Portland 97201.
FAU - North, R A
AU  - North RA
LA  - eng
GR  - DA03161/DA/NIDA NIH HHS/United States
GR  - DK32979/DK/NIDDK NIH HHS/United States
GR  - HL38940/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Proc R Soc Lond B Biol Sci
JT  - Proceedings of the Royal Society of London. Series B, Biological sciences
JID - 7505889
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 4S9CL2DY2H (Brimonidine Tartrate)
RN  - MN3L5RMN02 (Clonidine)
RN  - RWP5GA015D (Potassium)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Algorithms
MH  - Animals
MH  - Brimonidine Tartrate
MH  - Clonidine/pharmacology
MH  - Electric Conductivity
MH  - Guinea Pigs
MH  - Membrane Potentials
MH  - Norepinephrine/*pharmacology
MH  - Potassium/metabolism
MH  - Quinoxalines/pharmacology
MH  - Receptors, Adrenergic, alpha/*metabolism
MH  - Synapses/*drug effects
EDAT- 1988/06/22 00:00
MHDA- 1988/06/22 00:01
CRDT- 1988/06/22 00:00
PHST- 1988/06/22 00:00 [pubmed]
PHST- 1988/06/22 00:01 [medline]
PHST- 1988/06/22 00:00 [entrez]
AID - 10.1098/rspb.1988.0039 [doi]
PST - ppublish
SO  - Proc R Soc Lond B Biol Sci. 1988 Jun 22;234(1274):85-114. doi: 
      10.1098/rspb.1988.0039.