The lecture by S.Z. Langer, delivered at the Sixth Gaddum Memorial Lecture, focuses on the presence and role of presynaptic receptors in noradrenergic nerve endings and their regulation of neurotransmitter release. The introduction highlights the historical context, particularly the contributions of Sir John Gaddum to the understanding of neurotransmission. The main body of the lecture discusses the discovery and significance of presynaptic α-adrenoceptors, which play a crucial role in regulating noradrenaline release through a negative feedback mechanism. This mechanism is activated when noradrenaline concentration reaches a threshold, inhibiting further release. The lecture also explores the existence of presynaptic β-adrenoceptors, which mediate a positive feedback mechanism, enhancing noradrenaline release at low frequencies of nerve stimulation. The lecture concludes with a discussion on other types of presynaptic receptors and their potential roles in noradrenergic neurotransmission, emphasizing the importance of these receptors in both physiological and pharmacological contexts.The lecture by S.Z. Langer, delivered at the Sixth Gaddum Memorial Lecture, focuses on the presence and role of presynaptic receptors in noradrenergic nerve endings and their regulation of neurotransmitter release. The introduction highlights the historical context, particularly the contributions of Sir John Gaddum to the understanding of neurotransmission. The main body of the lecture discusses the discovery and significance of presynaptic α-adrenoceptors, which play a crucial role in regulating noradrenaline release through a negative feedback mechanism. This mechanism is activated when noradrenaline concentration reaches a threshold, inhibiting further release. The lecture also explores the existence of presynaptic β-adrenoceptors, which mediate a positive feedback mechanism, enhancing noradrenaline release at low frequencies of nerve stimulation. The lecture concludes with a discussion on other types of presynaptic receptors and their potential roles in noradrenergic neurotransmission, emphasizing the importance of these receptors in both physiological and pharmacological contexts.