Regulation of GABAB receptors by histamine and neuronal activity in the isolated spinal cord of neonatal opossum in culture

The aim of these experiments has been to analyse the properties of receptors for the transmitter γ -aminobutyric acid (GABA) in developing mammalian nervous system. Changes in responses of GABA B receptors have been measured after alterations of the chemical environment and the level of electrical activity. We have previously shown that when the central nervous system (CNS) of the new-born opossum, Monodelphis domestica , is cultured for three to five days in the presence of histidine, inhibition by baclofen, a GABA B agonist, disappears (Stewart et al . 1991). We have now investigated whether histidine acts indirectly by way of conversion to histamine. As with histidine, culture with 150 μ m histamine for five days virtually abolished the inhibition by baclofen. The effects of histidine, as well as histamine, were blocked by mepyramine, a histamine H 1 -receptor antagonist, and by ranitidine, an H 2 -antagonist. Tetrodotoxin (TTX), which blocks all electrical activity, protected preparations from the action of histidine but not histamine. Our results suggest that histidine is converted to histamine, which reduces the efficacy of GABA B agonists. We conclude that, in the developing mammalian CNS, transmitter levels and electrical activity can selectively influence the properties of receptors.