Tetrapeptides on N- and C-terminal regions of mastoparan inhibit catecholamine release from chromaffin cells by blocking nicotinic acetylcholine receptor.
Mastoparan (MP), a tetradecapeptide in wasp venom, has been reported to evoke catecholamine release, but also reported to inhibit secretory response upon nicotinic stimulation in adrenal chromaffin cells. To elucidate the inhibitory mechanism of MP, we examined the effect of two MP fragments (INLK-NH2 and KKIL-NH2) on catecholamine release in bovine adrenal chromaffin cells. These MP fragments inhibited catecholamine release induced by nicotinic stimulation in a noncompetitive manner. These fragments did not affect catecholamine release evoked by high [K+] or by other secretagogues, neither caused catecholamine release by themselves. Replacement by hydrophobic and basic amino acids of the MP fragments enhanced the inhibitory effects on ACh-evoked catecholamine release. Among 23 analogs of the MP fragments, (Nle)3-R-NH2 showed the most potent inhibition with IC50 = 541 microM. These results suggested that the MP fragments selectively inhibit the secretory response to nicotinic stimulation by attacking nAChR on the site(s) made up of hydrophobic and acidic amino acids but other than ACh-binding sites. This mechanism may explain the inhibitory action of MP on nicotine-evoked catecholamine release.
Monoi
Noriyuki
N
Graduate School of Science and Engineering, Aoyama Gakuin University, Fuchinobe, Sagamihara, Kanagawa, Japan. monoi1@lion.co.jp
Usui
Masaya
M
Takahashi
Shunichi
S
Ito
Hisashi
H
Kumakura
Konosuke
K
Kasai
Hisataka
H
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D036341:Intercellular Signaling Peptides and Proteins; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014862:Wasp Venoms / Q000737:chemistry / Q000494:pharmacology*
D000596:Amino Acids; D002395:Catecholamines; D036341:Intercellular Signaling Peptides and Proteins; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D011978:Receptors, Nicotinic; D014862:Wasp Venoms; C037500:mastoparan; D011188:Potassium