title: Limitations of presynaptic theory: no support for feedback control of autonomic effectors.
abstract: Only limited evidence, much of it repetitious, has supported the hypothesis that transmitter release is regulated by negative and positive feedback. It is shown here that the theory fails to satisfactorily predict the outcome of experimental tests that examine transmitter efflux critically, over an array of test conditions in several effector organs. Experimentally established inadequacies relate to: the observed effects of agonists and antagonists on stimulation-induced efflux; presynaptic site specificity; per pulse output of transmitter in the absence and presence of drugs; single-pulse stimulation; synaptic dimensions and efflux; lack of coincidence between enhancement of efflux and blockade of amine-induced inhibition and between effector response size and efflux alterations. Theoretical considerations about negative and positive feedback that render their routine operation unlikely are also discussed. It is concluded that, despite repeated observations that norepinephrine and some antagonists exert presynaptic actions to decrease and enhance transmitter output, the unitary hypothesis that assigns these effects to interactions with functional autoinhibitory and excitatory systems mediated by alpha- and beta-adrenergic receptors is probably not correct.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D005246:Feedback; D008959:Models, Neurological; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009451:Neuroeffector Junction / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D014316:Tritium; D015016:Yohimbine; D002118:Calcium; D009638:Norepinephrine