RT Journal Article
SR Electronic
T1 STERIC ASPECTS OF ADRENERGIC DRUGS. XV. USE OF ISOMERIC ACTIVITY RATIO AS A CRITERION TO DIFFERENTIATE ADRENERGIC RECEPTORS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 622
OP 633
VO 176
IS 3
A1 PATIL, P. N.
A1 PATEL, D. G.
A1 KRELL, R. D.
YR 1971
UL http://jpet.aspetjournals.org/content/176/3/622.abstract
AB A new criterion is introduced to differentiate adrenergic receptors. It is postulated that if alpha adrenergic receptors in various tissues are of a single type, under proper experimental conditions, the isomeric activity ratio should be the same in these tissues. Conversely, if beta adrenergic receptors in various tissues are dissimilar, the isomeric activity ratios should be different. Thus, similarity of isomeric activity ratios of an agonist from different tissues is taken as evidence for the similarity of the receptor sites involved. Optical isomers of norepinephrine were selected for the purpose. Under normal circumstances the activity difference between the isomers is obscured by several factors. Although in some tissues catechol-O-methyltrans- ferase may be important, the density of adrenergic innervation appears to be the most important factor. In the normal tissue, the higher the density of adrenergic innervation, the lesser will appear the difference between the activity of (—)-and (+)-norepinephrine. When "uptake" was blocked by cocaine (in the presence of a catechol-O-methyltransferase inhibitor and a beta receptor blocking agent) the activity difference between (-)— (+)-norepinephrine was the same (approximately 300-fold) from six different tissues examined. Thus, it appears that alpha adrenergic receptors of rabbit aorta, vena cava, ileum and spleen, rat vas deferens and seminal vesicle are of a single type. In the normal tissue or tissue pretreated with cocaine, tropolone and phentolamine, the isomeric activity ratios from rat, rabbit and guinea-pig atria, guinea-pig trachea, rabbit aorta and bovine iris sphincter were not the same. Results are discussed in light of similarities and dissimilarities of adrenergic receptors of various organs. © 1971 by The Williams & Wilkins Co.