EFFECTS OF THE AMPHIPHILIC PEPTIDES MASTOPARAN AND ADENOREGULIN ON RECEPTOR-BINDING, G-PROTEINS, PHOSPHOINOSITIDE BREAKDOWN, CYCLIC-AMP GENERATION, AND CALCIUM INFLUX

11. The amphiphilic peptide mastoparan is known to affect phosphoinosi tide breakdown, calcium influx, and exocytosis of hormones and neurotr ansmitters and to stimulate the GTPase activity of guanine nucleotide- binding regulatory proteins. Another amphiphilic peptide, adenoregulin was recently identified based on stimulation of agonist binding to A( 1)-adenosine receptors. 2. A comparison of the effects of mastoparan a nd adenoregulin reveals that these peptides share many properties. Bot h stimulate binding of agonists to receptors and binding of GTP gamma S to G proteins in brain membranes. The enhanced guanyl nucleotide exc hange may be responsible for the complete conversion of receptors to a high-affinity state, complexed with guanyl nucleotide-free G proteins . 3. Both peptides increase phosphoinositide breakdown in NIH 3T3 fibr oblasts. Pertussis toxin partially inhibits the phosphoinositide break down elicited by mastoparan but has no effect on the response to adeno regulin. N-Ethylmaleimide inhibits the response to both peptides. 4. I n permeabilized 3T3 cells, both adenoregulin and mastoparan inhibit GT P gamma S-stimulated phosphoinositide breakdown. Mastoparan slightly i ncreases basal cyclic AMP levels in cultured cells, followed at higher concentrations by an inhibition, while adenoregulin has minimal effec ts. 5. Both peptides increase calcium influx in cultured cells and rel ease of norepinephrine in pheochromocytoma PC12 cells. The calcium inf lux elicited by the peptides in 3T3 cells is not markedly altered by N -ethylmaleimide. 6. Multiple sites of action appear likely to underlie the effects of on receptors, G proteins, phospholipase C, and calcium .