Effect of Li+ substitution for extracellular Na+ on GRF-induced GH secretion from rat pituitary cells.
Several observations have been made on the mechanism of human growth hormone-releasing factor (hGRF)-induced growth hormone (GH) secretion. 1) hGRF activates adenylate cyclase and the production of adenosine 3',5'-cyclic monophosphate (cAMP). 2) Extracellular Ca2+ is indispensable in both hGRF- and excess K+-induced GH secretion. 3) Extracellular Na+ is also essential in hGRF-induced but not in excess K+-induced GH secretion. 4) Both Ca2+ and Na+ are required in dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-induced GH secretion. Thus hGRF may increase Na+ conductance via cAMP, which in turn depolarizes the somatotrophs and activates voltage-sensitive Ca2+ channels, thereby promoting Ca2+ entry and GH secretion. To further examine this possibility, replacement of Na+ with Li+ (an alkali metal ion permeant to Na+ channel) was studied in perifused dispersed rat anterior pituitary cells. Li+ substitution for extracellular Na+ did not suppress but augmented hGRF-and DBcAMP-induced GH secretion, whereas the rise in cellular cAMP content produced by hGRF was greatly attenuated in Na+-free, Li+ medium. This hGRF-induced GH secretion in Na+-free, Li+ medium was almost completely nullified by removing extracellular Ca2+. Thus Li+ was able to replace Na+, which further suggests the involvement of Na+ channels in hGRF-induced GH secretion. The possible mechanism of the augmented response in Na+-free, Li+ medium is discussed.
Kato
M
M
Department of Physiology, Gunma University, Maebashi, Japan.
Suzuki
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*
D010042:Ouabain; D003994:Bucladesine; D000584:Amiloride; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D008094:Lithium; D012964:Sodium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D011188:Potassium; D002118:Calcium