Prejunctional alpha2A-autoreceptors in the human gastric and ileocolic arteries.
This study was undertaken to determine the subtype of prejunctional alpha2-autoreceptors in human blood vessels. Segments of gastric and ileocolic arteries were incubated with [3H]noradrenaline and subsequently perifused with modified Krebs-Henseleit solution containing cocaine (12 microM). Five periods of electrical stimulation (S1-S5) were applied (1 Hz, 1 ms, 50 V for 1 min). Concentration-response curves for the facilitatory effect of eight alpha-adrenoceptor antagonists [rauwolscine, 2-[2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimbine, phentolamine, idazoxan, 2-(2',6'-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101), spiroxatrine and prazosin] were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, indicating the existence of alpha2-autoreceptors. The EC30% values of the antagonists (concentrations that increased the evoked overflow of tritium by 30%) were taken as a measure of affinity to the autoreceptors. Correlations between the pEC30% values obtained in the present study and the pKi values of the same antagonists at cloned human alpha2A-, alpha2B-, alpha2C-adrenoceptors expressed in Chinese hamster lung cells and at alpha2D-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the alpha2-autoreceptors in the human gastric and ileocolic arteries resemble most closely the alpha2A-subtype.
Guimarães
S
S
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Figueiredo
I V
IV
Caramona
M M
MM
Moura
D
D
Paiva
M Q
MQ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D017660:Autoreceptors / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
C547768:ADRA2A protein, human; C547770:Adra2a protein, rat; D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D004146:Dioxanes; D018492:Dopamine Antagonists; D018341:Receptors, Adrenergic, alpha-2; D013141:Spiro Compounds; D014316:Tritium; D015016:Yohimbine; C018387:spiroxatrine; C058525:2-methoxyidazoxan; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan; D010646:Phentolamine