GABAB receptors increase intracellular calcium concentrations in chromaffin cells through two different pathways: Their role in catecholamine secretion

Abstract

The activation of GABAB receptors of adrenal chomaffin cells produces an increase of [Ca2+]i measured by fura-2 AM techniques. GABAB agonists 3-aminopropylphosphinic acid or (-)baclofen, at concentrations of 0.5 mM, increased basal Ca2+ values 332 +/- 60.9 and 306 +/- 40.5 nM, respectively, in cells suspended in a 2.5 mM Ca2+ buffer. The GABAB-induced increase of [Ca2+]i seemed to have two different components. The first was due to an entry from the extracellular medium mainly through L-type voltage-dependent Ca2+ channels as the dihydropiridine nifedipine 50 microM was able to decrease it more than 60%, while omega-conotoxin, which blocks N-type channels, did not produce any change in the GABAB-evoked Ca2+ increment. The second component was due to a release of Ca2+ from intracellular pools and was about one-third of the total GABAB-induced increase of [Ca2+]i. GABAB receptors stimulated inositol 1,4,5-trisphosphate-sensitive and not the caffeine-sensitive Ca2+ store. In a low-Ca2+ buffer after treatment with 2 microM angiotensin II, neither 0.5 mM 3-APPA nor baclofen were able to produce an additional increase of [Ca2+]i, whereas 4 mM caffeine had no effect on GABAB response. This intracellular Ca2+ mobilization could be due to inositol 1,4,5-trisphosphate accumulation produced by the activation of GABAB receptors. In fact, the specific agonists after 10 minutes incubation produced a dose-dependent increase of inositol 1,4,5-trisphosphate. The maximal effect was obtained at 100 microM baclofen and 3-APPA, and it was 3.63 +/- 0.75 and 3.2 +/- 1.5 times the basal levels (7.3 +/- 0.3 pmol/10(6) cells), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)