Mechanisms for establishment of GABA signaling in adrenal medullary chromaffin cells

Abstract

γ-Aminobutyric acid (GABA) is thought to play a paracrine role in adrenal medullary chromaffin (AMC) cells. Comparative physiological and immunocytochemical approaches were used to address the issue of how the paracrine function of GABA in AMC cells is established. GABA A receptor Clchannel activities in AMC cells of rats and mice, where corticosterone is the major glucocorticoid, were much smaller than those in AMC cells of guinea-pigs and cattle, where cortisol is the major. The extent of enhancement of GABA A receptor α3 subunit expression in rat pheochromocytoma (PC12) cells by cortisol was larger than that by corticosterone in parallel with their glucocorticoid activities. Thus, the species difference in GABA A receptor expression may be ascribed to a difference in glucocorticoid activity between corticosterone and cortisol. GABA A receptor Clchannel activity in mouse AMC cells was enhanced by allopregnanolone, as noted with that in guinea-pig AMC cells, and the enzymes involved in allopregnanolone production were immunohistochemically detected in the zona fasciculata in both mice and guinea pigs. The expression of glutamic acid decarboxylase 67 (GAD67), one of the GABA synthesizing enzymes, increased after birth, whereas GABA A receptors already developed at birth. Stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, but not nicotinic or muscarinic receptors, in PC12 cells, resulted in an increase in GAD67 expression in a protein-kinase A-dependent manner. The results indicate that glucocorticoid and PACAP are mainly responsible for the expressions of GABA A receptors and GAD67 involved in GABA signaling in AMC cells, respectively.

Study on influence of external factors on the electrical excitability of PC12 quasi-neuronal networks through Voltage Threshold Measurement Method

“…As a commonly used anesthetic, LDH can act on TRPV1 and GABA receptors and further change the electrical excitability of neurons [31][32][33][34]. PC12 cells were also equipped with TRPV1 and GABA receptors [35][36][37]. The similarity between the effects of LDH on the electrical excitability of PC12 quasi-neuronal networks and that of the other two types of neuronal networks were highly probably caused by that they shared same types of receptors.…”