Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells.
We studied whether a novel proadrenomedullin derived peptide was present and what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of proadrenomedullin N-terminal 12 peptide (PAMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12 was added in the incubation medium, this peptide inhibited nicotinic receptor-mediated catecholamine release and influx of Na(+) and Ca(2+) into the cells. PAMP-12 did not affect catecholamine release evoked by histamine or by depolarization by high concentration of potassium. PAMP-12 also inhibited synthesis of catecholamines as well as the activation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamines by acting on nicotinic cholinergic receptors in an autocrine manner in adrenal chromaffin cells.
Kobayashi
H
H
Department of Pharmacology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. hkobayas@post.miyazaki-med.ac.jp
Yamamoto
R
R
Kitamura
K
K
Kuwasako
K
K
Minami
S
S
Yanagita
T
T
Shiraishi
S
S
Yokoo
H
H
Eto
T
T
Wada
A
A
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D053607:Adrenomedullin / Q000031:analogs & derivatives; D000818:Animals; D000906:Antibodies; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D018679:Cholinergic Agonists / Q000494:pharmacology; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides; D011506:Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D000906:Antibodies; D002250:Carbon Radioisotopes; D002395:Catecholamines; D018679:Cholinergic Agonists; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D011978:Receptors, Nicotinic; C108283:proadrenomedullin (9-20); D053607:Adrenomedullin; D002217:Carbachol; D012964:Sodium