Norepinephrine stimulates potassium efflux from pinealocytes: evidence for involvement of biochemical "AND" gate operated by calcium and adenosine 3',5'-monophosphate.
Biochemical studies of K+ efflux from rat pinealocytes revealed for the first time that norepinephrine (NE) increases 86Rb+ and 42K+ efflux. The effects of NE depend upon concurrent activation of both alpha 1- and beta-adrenoceptors. This effect is mediated by cAMP and Ca2+, which appear to act in conjunction to control K+ efflux; studies with charybdotoxin and tetraethylammonium indicate that a Ca2(+)-sensitive K+ channel (K(Ca] appears to be involved. Patch clamp studies identified a large conductance (approximately 100 psec) K+ channel. This study also revealed for the first time that NE treatment increases the fraction of time that this channel was open. Studies of inside-out pineal membrane patches indicated that increasing Ca2+ at the cytoplasmic surface of the membrane increased the frequency of channel opening, as is typical of K(Ca) channels in this type of preparation. Outward K+ currents were almost completely blocked by tetraethylammonium (10 mM) and scorpion venom (L. quinquestriatum; 100 ng/ml). Cell-attached studies confirm that the effects of NE are mediated by intracellular second messengers. These investigations suggest that NE elevates K+ flux, probably through a large conductance K(Ca) channel, that NE acts through alpha 1- and beta-adrenergic receptors, and that Ca2+ and cAMP act together through a biochemical "AND" gate to mediate the effects of receptor activation. Activation of this K(Ca) channel would have a hyperpolarizing influence and might contribute to the adrenergic hyperpolarization of pinealocytes.
Ceña
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V
Section on Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Halperin
J I
JI
Yeandle
S
S
Klein
D C
DC
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology*; D010052:Ovariectomy; D010870:Pineal Gland / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D015221:Potassium Channels; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000001:Calcimycin; D012964:Sodium; D011433:Propranolol; D000242:Cyclic AMP; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin