Masked excitatory action of noradrenaline on rat islet beta-cells via activation of phospholipase C.
The effect of noradrenaline (NE) on rat islet beta-cells was examined. NE reduced insulin secretion from rat islets exposed to extracellular solutions containing glucose at 5.5 or 16.6 mM. In islets treated with pertussis toxin (PTX), however, NE increased insulin secretion. The NE-induced augmentation of insulin secretion was inhibited by prazosin. In intact islets, NE increased phospholipase C (PLC) activity, an effect that was prevented by treatment of islets with U-73122. NE elevated intracellular [Ca2+] ([Ca2+]i) in isolated beta-cells independently of PTX. Although this NE effect was inhibited by prazosin, phenylephrine did not mimic it. The [Ca2+]i response to NE was also prevented by the treatment of cells with U-73122. NE produced depolarization of beta-cells followed by nifedipine-sensitive action potentials. NE reduced the whole-cell membrane currents through ATP-sensitive K+ channels (KATP), responsible for the depolarization. This NE effect was prevented by treatment of beta-cells with U-73122 or BAPTA/AM. Although at least some of our results imply the presence of alpha1-adrenoceptors, beta-cells were not stained by a polyclonal IgG antibody recognizing all adrenergic alpha1-receptor subtypes so far identified. These results suggest that an interaction of NE with an unknown type of receptor activates rat islet beta-cells via a PLC-dependent signal pathway. This effect is, however, masked by the inhibitory action via a PTX-sensitive pathway also activated by NE.
Department of Physiology, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562 Hirosaki, Japan.
Sechiko
S
Suga
Kyoko
K
Nakano
Teruko
T
Takeo
Tomohiro
T
Osanai
Yoshiji
Y
Ogawa
Soroku
S
Yagihashi
Takahiro
T
Kanno
Makoto
M
Wakui
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000378:metabolism*
D010738:Type C Phospholipases; D009638:Norepinephrine