Chromogranin A, dopamine β-hydroxylase and secretion from the adrenal medulla

Abstract

Studies of the biosynthesis, storage and secretion of catecholamines by the adrenal medulla have served as models for similar studies of the adrenergic neuron. For example, the synthesis of noradrenaline and the intracellular distribution of the biosynthetic enzymes was first described in the adrenal medulla and subsequently shown to be the same in sympathetic nerves (Blaschko 1939; Kirshner 1957, 1959; Levin, Levenberg & Kaufman i960; Potter & Axelrod 1963; Nagatsu, Levitt & Udenfriend 1964; Stjarne & Lishajko 1966; Oka et al. 1967; Musacchio 1968; Laduron & Belpaire 1968). The storage vesicles of the adrenal medulla have counterparts in the synaptic vesicles (Blaschko & Welch 1953; Hillarp, Lagerstedt & Nilson 1953; von Euler & Hillarp 1956; Schumann 1958) and the incorporation of catecholamines into the storage vesicles, and the storage complex itself, seems to be similar in both tissues, (Kirshner 1962; Carlsson, Hillarp & Waldeck 1963; von Euler & Lishajko 1963; von Euler, Lishajko & Stjarne 1963; Stjarne 1964). Recently it has been demonstrated that proteins specifically localized in the storage vesicles of the adrenal medulla are also present in the storage vesicles of sympathetic nerve endings (Hopwood 1967, 1968; Geffen, Livett & Rush 1969; Banks, Helle & Major 1969; de Potter, de Schaepdryver, Moerman & Smith 1969). There are obvious differences between the two types of vesicles (Stjarne 1964; Potter 1967), but the similarities are such as to suggest that the vesicles from both tissues serve the same physiological functions—to synthesize and store adrenaline or noradrenaline and to release these compounds in response to neural stimulation. Secretion from the adrenal medulla appears to be a good model for release of neurotransmitters at synapses in the sense that it provides and suggests experimental approaches to the problem (Geffen et al. 1969; de Potter et al. 1969). In general, the secretion of substances which are synthesized in cells and stored in subcellular organelles have many features in common (Douglas 1968; Stormorken 1969) and release of neurotransmitters at synapses may be another example of this generalized biological process. During the past few years, evidence has been presented from several laboratories that secretion from the adrenal medulla occurs by exocytosis. The simultaneous release of catecholamines, adenine nucleotides, chromogranins and soluble dopamine β-hydroxylase contained within the storage vesicles and the retention of dopamine-β- hydroxylase firmly bound to the vesicle membrane have provided critical information on this secretory process.