title: Blockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors.
abstract: The blockade of exocytosis induced by the putative endogenous ligand for imidazoline receptors, agmatine, was studied by using on-line measurement of catecholamine release in bovine adrenal medullary chromaffin cells. Agmatine inhibited the acetylcholine-evoked release of catecholamines in a concentration-dependent manner (IC(50)=366 microM); the K(+)-evoked release of catecholamines was unaffected. Clonidine (100 microM) and moxonidine (100 microM) also inhibited by 75% and 50%, respectively, the acetylcholine-evoked response. In cells voltage-clamped at -80 mV, the intermittent application of acetylcholine pulses elicited whole-cell inward currents (I(ACh)) that were blocked 63% by 1 mM agmatine. The onset of blockade was very fast (tau(on) = 31 ms); the recovery of the current after washout of agmatine also occurred very rapidly (tau(off = 39 ms). Efaroxan (10 microM) did not affect the inhibition of I(ACh) elicited by 1 mM agmatine. I(ACh) was blocked 90% by 100 microM clonidine and 50% by 100 microM moxonidine. The concentration-response curve for acetylcholine to elicit inward currents was shifted to the right in a non-parallel manner by 300 microM agmatine. The blockade of I(ACh) caused by agmatine (100 microM) was similar at various holding potentials, around 50%. When intracellularly applied, agmatine did not block I(ACh). At 1 mM, agmatine blocked I(Na) by 23%, I(Ba) by 14%, I(K(Ca)) by 16%, and I(K(VD)) by 18%. In conclusion, agmatine blocks exocytosis in chromaffin cells by blocking nicotinic acetylcholine receptor currents. In contrast to previous views, these effects seem to be unrelated to imidazoline receptors.
authors: Departamento de Farmacología, Escola Paulista de Medicina, UNIFESP, 04034-970, SP, Sao Paulo, Brazil.
authors: W C
authors: WC
authors: Santos
authors: J M
authors: JM
authors: Hernández-Guijo
authors: A
authors: A
authors: Ruiz-Nuño
authors: R
authors: R
authors: Olivares
authors: A
authors: A
authors: Jurkiewicz
authors: L
authors: L
authors: Gandía
authors: A G
authors: AG
authors: García
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000376:Agmatine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
chemical_list: D001572:Benzofurans; D015220:Calcium Channels; D002395:Catecholamines; D007093:Imidazoles; D054755:Imidazoline Receptors; D015221:Potassium Channels; D011955:Receptors, Drug; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D000376:Agmatine; C043482:moxonidine; C062597:efaroxan; D003000:Clonidine; D000109:Acetylcholine; D011188:Potassium