Dopamine was injected intravenously (9 μg/kg) or intraperitoneally (15 μg/kg) to Wistar rats (3-4 months, 300-400 g). Hepatocytes were isolated 40 min after dopamine injection. Dense cultures were maintained on collagen-coated glasses. By the 5th hour, the circaholarian rhythm of protein synthesis in hepatocytes cultures was absent in the dopamine group, but was present in cultures from animals receiving physiological saline (NaCl). The rhythm-disorganizing effect of dopamine was reversible. The rhythm was observed in cultures of hepatocytes isolated 1 day after dopamine treatment. The effect of dopamine was abolished by melatonin. The protein synthesis rhythm was revealed in 5-h cultures of hepatocytes from rats receiving melatonin (32 ng/kg) 40 min after intraperitoneal injection of dopamine. The results of our in vitro experiments with addition of dopamine into the medium of cultured hepatocytes [1] suggest that dopamine in vivo produces a direct effect on liver cells. The observed changes are discussed taking into account the biochemical mechanisms for a direct cell-cell interaction and previously unknown properties of catecholamines.
We studied dense 24-hour cultures of rat hepatocytes in serum-free medium on collagen-coated slides. As before, a circahoralian rhythm of protein synthesis was observed in control cultures in a fresh medium. No rhythm was found after addition of 1-10 μM dopamine to the medium containing such cultures. The rhythm was observed after addition of 0.3 μM ganglioside to pretreated-dopamine cultures. Dopamine is likely to influence the conditioning of intercellular medium with gangliosides. Deficit of this endogenous synchronizing factor in the intercellular medium blocks self-organization of the protein synthesis rhythm. Thus, in contrast to previously studied norepinephrine and serotonin, as well as gangliosides, which organized the population rhythm of protein synthesis, dopamine disorganized the rhythm, impairing direct intercellular interactions.
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