Prejunctional alpha2A-autoreceptors in the canine saphenous vein.
The aim of the study was to determine the subtype of prejunctional alpha2-autoreceptors in the canine saphenous vein. Segments of the vein were incubated with 3H-noradrenaline and subsequently perifused with modified Krebs-Henseleit solution. Five periods of electrical stimulation were applied (S1-S5; each for 2 min, 1 Hz). Concentration-response curves for the inhibitory effect of the alpha2-adrenoceptor agonists oxymetazoline and UK-14,304 and for the facilitatory effect of nine antagonists were determined. Correlations between the pEC30%s for the antagonists obtained in the present study and the pKis for the same antagonists obtained in tissues expressing only alpha2A- (HT29 cells), alpha2B- (neonatal rat lung), alpha2C- (OK cells) or alpha2D-adrenoceptors (rat submaxillary gland) showed that the alpha2-autoreceptors in the canine saphenous vein resemble most closely the alpha2A-subtype. Furthermore, oxymetazoline was a highly potent agonist (pIC50% = 8.10) and prazosin was a weak antagonist (pEC30% = 6.46), confirming that the alpha2-adrenoceptors involved in the modulation of the response to electrical stimulation of the canine saphenous vein do not belong to either the alpha2B- or alpha2C-subtype. On the other hand, the EC30% ratios phentolamine/rauwolscine and idazoxan/rauwolscine were much closer to the ratios obtained at alpha2-autoreceptors of the rabbit- (alpha2A) than of the guinea-pig brain cortex (alpha2D). The results suggest that the sympathetic nerves of the canine saphenous vein are endowed with alpha2A-adrenoceptors.
Paiva
M Q
MQ
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Alameda Hernani Monteiro, Porto, Portugal.
Mota
A
A
Moura
D
D
Guimarães
S
S
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
C547770:Adra2a protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D009638:Norepinephrine