Maxadilan specifically interacts with PAC1 receptor, which is a dominant form of PACAP/VIP family receptors in cultured rat cortical neurons

Maxadilan is a potent vasodilator peptide isolated from salivary gland extr acts of the hematophagous sand fly. Recently, the possibility was demonstra ted that maxadilan binds to PAC1 receptor (PACAP pituitary adenylate cyclas e activating polypeptide type I receptor) in mammals. In the present study, we demonstrated that: (1) maxadilan specifically binds to PAC1 receptor an d stimulates cyclic AMP accumulation in a dose-dependent manner in CHO cell s stably expressing PAC1 receptor, not VIP (vasoactive intestinal polypepti de) receptors; that (2) the deleted peptide (amino acid #24-42) of maxadila n (termed max.d.4) also specifically binds to PAC1 receptor although max.d. 4 inhibits cyclic AMP accumulation stimulated by both maxadilan and PACAP: and that (3) max.d.4 completely blocks the cyclic AMP accumulation induced by VIP in cultured rat cortical neurons. The expression of specific PACAP r eceptors in cultured rat cortical neurons was further investigated by the r everse transcription-polymerase chain reaction technique, which showed the presence of mRNA coding for PAC1 receptor among PACAP/VIP family receptors. These data indicate that maxadilan and max.d.4 represent important tools f or clarifying the physiological role of PAC1 receptor, and that PAC1 recept or plays an important role in the regulation of the functions induced by PA CAP in rat cultured cortical neurons. (C) 2001 Elsevier Science B.V. All ri ghts reserved.