Pathophysiological function of adrenomedullin and proadrenomedullin N-terminal peptides in adrenal chromaffin cells.
Adrenomedullin (AM) and peptides of the proadrenomedullin N-terminal 20 peptide (PAMP20) family are multifunctional peptides abundantly expressed in the adrenal medulla. These peptides are released by regulated exocytosis along with catecholamines upon stimulation of adrenal chromaffin cells. They are also released gradually during culture, and this release is stimulated by a 3',5'-cyclic adenosine monophosphate (cAMP)-dependent pathway. The expression and release of AM increase under hypoxia in chromaffin cells. The expression of AM in pheochromocytoma PC12 cells is reduced during neuronal differentiation with nerve growth factor. On the other hand, PAMP20 and PAMP12 suppress catecholamine release and synthesis by interfering with nicotinic cholinergic receptors. AM increases blood flow in the adrenal gland, and causes a gradual release of catecholamine, but does not modify regulated exocytosis upon the stimulation of cells. Current data indicate that the expression of these peptides is regulated by intracellular signaling pathways, and changes under various physiological and pathological conditions. AM and PAMP20 family peptides have distinct physiological functions. PAMP20 and PAMP12 are endogenous peptides that modulate chromaffin cell function in an autocrine manner, whereas AM may mainly regulate vascular cell function in a paracrine manner.
Kobayashi
Hideyuki
H
Department of Pharmacology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. hkobayas@post.miyazaki-med.ac.jp
Yanagita
Toshihiko
T
Yokoo
Hiroki
H
Wada
Akihiko
A
D000313:Adrenal Medulla / Q000166:cytology / Q000503:physiopathology*; D053607:Adrenomedullin; D000818:Animals; D019439:Chromaffin Cells / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D010455:Peptides / Q000502:physiology*; D011506:Proteins / Q000502:physiology
D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D053607:Adrenomedullin