Inhibition of voltage-dependent Ca2+ channels via ?2-adrenergic and opioid receptors in cultured bovine adrenal chromaffin cells

Abstract

Adrenal chromaffin cells secrete catecholamines and opioids. The effects of these agents on whole-cell Ca2+ channel currents were studied, using bovine adrenal chromaffin cells kept in short term culture. Ca2+ channel currents recorded during voltage-clamp pulses from a holding potential of -80 mV to 0 mV were reversibly reduced by 10 microM epinephrine (in the presence of 1 microM propranolol) or 5 microM of the synthetic opioid, d-Ala2-d-Leu5-enkephalin (DADLE) by approximately 35% and 25%, respectively. The inhibitory action of epinephrine was mimicked by clonidine, reduced by yohimbine but not affected by prazosin. The DADLE-induced reduction of the Ca2+ channel current was antagonized by naloxone. The dihydropyridine (+)PN 200-110 (5 microM) reduced the Ca2+ channel current by approximately 40%; the Ca2+ channel current inhibited by (+)PN 200-110 was not further reduced by epinephrine. Intracellular infusion of guanosine-5'-O-(2-thiodiphosphate) and pretreatment of cells with pertussis toxin abolished the inhibitory effect of both epinephrine and DADLE. In membranes of adrenal chromaffin cells, four pertussis-toxin-sensitive G-proteins were identified, including Gi1, Gi2, Go1 and another Go subtype, possibly Go2. The data show that activation of alpha 2-adrenergic and opioid receptors causes an inhibition of dihydropyridine-sensitive Ca2+ channels in adrenal chromaffin cells. These inhibitory modulations are mediated by pertussis-toxin-sensitive G-proteins and may represent a mechanism for a negative feedback signal by agents released from the adrenal medulla.

Multiple Pathways for ATP-lnduced Intracellular Calcium Elevation in Pheochromocytoma (PC12) Cells

“…We used specific Ca3 channel block ers to identify three components of the whole Ca3 channel current; a DHP-and toCTX-sensitive (L"-type channel), a wCTX-sensitive but DHP-insensitive (N-type channel), and a DHP-and coCTX-insensitivc component. Recently, we have obtained similar results in bovine chro maffin cells [14].…”

Histamine promotes excitability in bovine adrenal chromaffin cells by inhibiting an M-current

“…However, histamine has been shown in bovine chromaffin cells to cause a reduction in Ca 2+ currents through a pertussis toxin-insensitive pathway (Currie & Fox, 2000). As it has also been suggested that feedback of released transmitters may also inhibit Ca 2+ currents in bovine chromaffin cells (Doupnik & Pun, 1994), a phenomenon that could be due to activation of either a 2 -adrenergic (Kleppisch et al 1992), opioid (Albillos et al 1996) or P2Y purinergic receptors (Gandia et al 1993;Powell et al 2000), it is unclear whether this inhibitory effect of histamine on Ca 2+ currents is direct or indirect. Regardless, it is possible that a mechanism causing a reduction in Ca 2+ currents may also contribute to the observed reduction in action potential amplitude.…”

Facilitatory coupling between a glutamate metabotropic receptor and dihydropyridine-sensitive calcium channels in cultured cerebellar granule cells

“…The latter effect is likely coupled by a G,-like protein. It has been clearly established that G,, a pertussis toxin-sensitive G protein, negatively controls L-type Ca channels in neuroblastoma glioma hybrid cells (Hescheler et al, 1987) and anterior pituitary cells (Lledo et al, 1992) and may do so in adrenal chromaffin cells (Kleppisch et al, 1992;see Schultz et al, 1990, for a review). Brabet et al (1988) have shown that G, is expressed in cerebellar granule cells.…”