Investigation of the subtype of alpha 2-adrenoceptor mediating prejunctional inhibition of cardioacceleration in the pithed rat heart.
1. We have investigated the subtype of alpha 2-adrenoceptor mediating prejunctional inhibition of cardioacceleration in the pithed rat heart in comparison with alpha 2-adrenoceptor ligand binding sites. 2. In pithed rats, prejunctional alpha 2-adrenoceptors were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the inhibitory potency of the alpha 2-adrenoceptor agonist, xylazine, against the tachycardia to a single electrical stimulus given via the pithing rod. 3. Antagonist potency at prejunctional alpha 2-adrenoceptors in pithed rat heart was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of rat kidney and submandibular gland labelled with [3H]-yohimbine. 4. The correlation with the prejunctional alpha 2-adrenoceptor in pithed rat heart was best for the alpha 2D-adrenoceptor ligand binding site of rat submandibular gland (r = 0.98, n = 10, P < 0.0001), as compared to correlations with the alpha 2A-adrenoceptor ligand binding site of human platelet (r = 0.90, n = 9, P < 0.001), the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.82, n = 10, P < 0.01) and with published results for the alpha 2C-adrenoceptor ligand binding site (r = 0.48, n = 6, NS). 5. It is concluded that the functional prejunctional alpha 2-adrenoceptor of pithed rat heart closely resembles the alpha 2D-adrenoceptor ligand binding site of rat submandibular gland.
Smith
K
K
Department of Physiology, Royal College of Surgeons in Ireland, Dublin.
Gavin
K
K
Docherty
J R
JR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D014991:Xylazine / Q000378:metabolism; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D014991:Xylazine; D015016:Yohimbine