Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

Inositol trisphosphate (IP3), a product of the phosphoinositide cycle, mobilizes intracellular Ca2+ in many cell types. New evidence suggests that inositol tetrakisphosphate (IP4), an IP3 derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP4 are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP4 in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine (0.4 mM) stimulated an increase in 3H]IP4 and 3H]IP3 accumulation in chromaffin cells and this effect was completely blocked by atropine (0.5 mM). 3H]IP4 accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP3 and IP4 hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP4 and calcium homeostasis.