title: N-ethylmaleimide diminishes alpha 2-adrenoceptor-mediated effects on norepinephrine release in rat tail arteries.
abstract: Isolated tail arteries from Wistar rats, prelabeled with [3H]norepinephrine (NE) were subjected to electrical field stimulation (24 pulses at 0.4 Hz and 200 mA). Both NE release and vasoconstriction were measured in parallel. The selective alpha 2-adrenoceptor agonist B-HT 933 diminished the evoked NE release in a concentration-dependent manner. This effect of B-HT 933 was counteracted by the selective alpha 2-adrenoceptor antagonist rauwolscine, which given alone enhanced evoked transmitter release, indicating the presence of autoinhibition. N-Ethylmaleimide (NEM) (3 microM), which also in itself increased transmitter release, virtually abolished facilitation of release by 0.1 microM rauwolscine and diminished its inhibition by 10 microM B-HT 933. The diminution of the inhibitory effect of B-HT 933 was even more pronounced when the current strength was decreased from 200 mA to 90 mA to compensate for the NEM-induced increase in transmitter release. Treatment of the arteries with NEM did not affect the perfusion pressure. In contrast, however, the B-HT 933-induced increase in basal perfusion pressure was significantly diminished by NEM. Although 10 microM B-HT 933 given alone did not affect stimulation-evoked vasoconstriction, it caused a significant increase in arteries treated with NEM. In conclusion, the observed NEM-sensitivity of the presynaptic and vascular alpha 2-adrenoceptor mechanisms is compatible with the idea that both pre- and postsynaptic alpha 2-adrenoceptors couple to Pertussis toxin (PTX)-sensitive G proteins.
authors.affiliation: Department of Pharmacology, University of Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Allgaier
authors.forename: H D
authors.initials: HD
authors.lastname: Weber
authors.forename: G
authors.initials: G
authors.lastname: Hertting
authors.forename: P
authors.initials: P
authors.lastname: Illes
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005033:Ethylmaleimide / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; C015603:azepexole; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide; D009638:Norepinephrine