Noradrenaline release from cultured mouse postganglionic sympathetic neurons: autoreceptor-mediated modulation.
The possible existence of alpha2-autoreceptors, P2-autoreceptors, and adenosine A1- or A2A-receptors was studied in cultured thoracolumbar postganglionic sympathetic neurons from mice. The cells were preincubated with [3H]noradrenaline and then superfused. The selective alpha2-adrenoceptor agonist UK 14,304 reduced the electrically evoked overflow of tritium. When the cultures were stimulated by trains of increasing pulse number, ranging from a single pulse to 72 pulses at 3 Hz, the concentration-inhibition curve of UK 14,304 was shifted progressively to the right and the maximal inhibition obtainable became progressively smaller. Six alpha-adrenoceptor antagonists shifted the concentration-inhibition curve of UK 14,304 in a parallel manner to the right. Neither ATP (3-300 microM), adenosine (0.01-100 microM), the selective A1-receptor agonist cyclopentyladenosine (1-1,000 nM), nor the selective A2A-receptor agonist CGS-21680 (1-10,000 nM) changed the basal or the electrically evoked overflow of tritium. It is concluded that the cultured neurons possess presynaptic, release-inhibiting alpha2-autoreceptors. As in intact tissues, the effectiveness of presynaptic alpha2-adrenergic inhibition depends on the "strength" of the releasing stimulus. The pK(D) values of the six antagonists against UK 14,304 indicate that the autoreceptors belong to the pharmacological alpha2D and hence the genetic alpha(2A/D) subtype of alpha2-adrenoceptor. Neither P2-autoreceptors nor receptors for adenosine, the degradation product of ATP, were detected.
Trendelenburg
A U
AU
Pharmakologisches Institut, Universität Freiburg, Freiburg im Breisgau, Germany.
Cox
S L
SL
Gaiser
E G
EG
Meyer
A
A
Starke
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D002478:Cells, Cultured; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D006801:Humans; D019329:Idazoxan / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011810:Quinoxalines / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015016:Yohimbine; C048599:N(6)-cyclopentyladenosine; D000068438:Brimonidine Tartrate; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine; D019329:Idazoxan; D010646:Phentolamine