Regarding the unitary theory of agonist and antagonist action at presynaptic adrenoceptors.
1. The linkage between potentiation of field stimulation-induced noradrenaline release and blockade of the presynaptic inhibitory effect of exogenous noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta preparations. 2. Rauwolscine clearly potentiated the release of noradrenaline in response to 100 pulses at 2 Hz but reduced the capacity of noradrenaline to inhibit transmitter release to a questionable extent, and then only when comparisons were made with untreated, rather then to rauwolscine-treated, controls. 3. Aortic preparations exposed for 60 min to rauwolscine followed by superfusion with antagonist-free Krebs for 60 min retained the potentiation of stimulation-induced transmitter release but no antagonism of the noradrenaline-induced inhibition could be detected at either of two noradrenaline concentrations when comparisons were made with rauwolscine treated controls. 4. Comparisons of the inhibitory effect of exogenous noradrenaline (1.8 x 10-6 M) on transmitter efflux in the presence and absence of rauwolscine pretreatment revealed that the antagonist enhanced rather than antagonized the presynaptic inhibition by noradrenaline. 5 It is concluded that the unitary hypothesis that asserts that antagonist enhancement of transmitter release and its blockade of noradrenaline induced inhibition are manifestations of a unitary event are not supportable.
Kalsner
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S
Department of Physiology and Pharmacology, CUNY Medical School/Sophie Davis School of Biomedical Education, City College of New York, New York City, NY 10031, USA.
Abdali
S A
SA
D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D017661:Receptors, Presynaptic; D009638:Norepinephrine