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Platelet monoamine oxidase (MAO) activity was significantly lower than control values in a subgroup of 16 schizophrenic patients (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other schizophrenic patients without auditory hallucinations. This finding suggests that reduced platelet MAO activity is not found in all schizophrenic patients but tends to occur in a clinically identifiable subgroup.

Major increases in the serotonin concentrations of rat pineal organs were produced by administering Catron, a monoamine oxidase inhibitor, prior to autopsy, or by preincubating the glands with serotonin (3X10-4M). These increases had no effect on pineal uptake of H3-tryptophan, the amino acid precursor for serotonin. These observations provide further evidence that the control of serotonin synthesis involves an important "open-loop" component.

Astrocytes in cultures of brain cells from fetal or newborn hamsters undergo neoplastic transformation after infection with simian virus 40 or polyoma virus. Subcutaneous or intracerebral inoculation of the transformed brain cells into newborn or adult hamsters produces progressively enlarging astrocytomas at the sites of injection. Astrocytomas produced by polyomatransformed cell lines are histologically better differentiated, but grow more rapidly and metastasize more frequently, than astrocytomas produced by cell lines transformed by simian virus 40. These observations make available in vitro models of virus-induced oncogenesis in astrocytes and provide simple techniques for obtaining astrocytoma cell lines suitable for screening studies of chemical agents effective against astrocytomas.

Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine.

Previous work has shown that the activity of the melatonin-forming enzyme in the rat pineal gland is elevated in rats kept in continuous darkness as compared to those kept in continuous light. Information about environmental lighting reaches the pineal gland via nerves that liberate noradrenaline. Rat pineal glands in organ culture can form C(14)-melatonin from C(14)-tryptophan as follows: tryptophan --> 5-hydroxytryptophan --> serotonin --> melatonin. Noradrenaline was found to stimulate the synthesis of C(14)-melatonin from C(14)-tryptophan in rat pineals in organ culture. Other compounds related in structure to noradrenaline increase melatonin and serotonin synthesis and inhibit the formation of the deaminated product of serotonin, 5-hydroxyindole acetic acid. Cycloheximide, a compound that inhibits protein synthesis, also prevents the formation of serotonin, melatonin, and 5-hydroxyindole acetic acid from tryptophan in pineal organ culture. These observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing the formation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.

Organ cultures of individual rat pineals incorporate (14)C-tryptophan into proteins at a nearly constant rate for at least 48 hours. Previous studies have shown that these cultures also convert (14)C-tryptophan to serotonin, melatonin, and 5-hydroxyindoleacetic acid, and release these indoles into the media. The formation of (14)C-protein from (14)C-tryptophan is accelerated by the addition to the culture medium of l-norepinephrine or related catecholamines but is not modified by serotonin, melatonin, or 5-hydroxyindoleacetic acid. One mechanism by which norepinephrine stimulates the synthesis of (14)C-protein from (14)C-tryptophan involves increasing the uptake of the (14)C-tryptophan into pineal parenchymal cells, inasmuch as (1) norepinephrine increases the intracellular content of (14)C-tryptophan as well as its conversion to its major products, (14)C-protein and (14)C-indoles; (2) norepinephrine does not stimulate (14)C-protein synthesis in pineal organs which contain a previously fixed amount of (14)C-tryptophan; and (3) norepinephrine does not stimulate (14)C-protein synthesis from (14)C-methionine or (14)C-leucine. The finding that norepinephrine, but not serotonin, can stimulate the incorporation of (14)C-tryptophan into pineal proteins is consistent with the hypothesis that norepinephrine is the neurotransmitter substance utilized by pineal sympathetic nerve endings.

The soluble supernatant fraction of homogenates of cloned rat astrocytoma cells (linle C-2A) was subjected to polyacrylamide gel electrophoresis. Two peaks of adenosine 3',5'-monophosphate phosphodiesterase activity were found, corresponding to peaks I and IV of a similarly prepared homogenate of rat brain. Incubating cells with norepinephrine (0.3 mullimolar) caused about a threefold increase in the activity of peak IV but no change in peak I. This increase was completely inhibited by prior inclubation with propranolol (0.1 millimnolar), a beta-adrenergic blocking agent, or with cyclohexamnine (40 micromolar). a protein synthesis inhibitor. Induction of a specific phosphodiesterase form by norepinephrine sitggests another feedback control mechanism whereby an organism can prevent the effects of excessive sympathetic activity.