Amylin-induced suppression of ANP secretion through receptors for CGRP1 and salmon calcitonin.
Amylin cosecretes with insulin from pancreatic beta-cells and shows high sequence homology with CGRP, adrenomedullin, and salmon calcitonin. This study aimed to investigate the effect of amylin on the atrial hemodynamics and ANP release from rat atria and to identify its receptor subtypes. Isolated perfused left atria from either control or streptozotocin-treated rats were paced at 1.3 Hz. The concentration of ANP was measured by radioimmunoassay and the translocation of ECF was measured by [3H]-inulin clearance. Rat amylin increased atrial contractility and suppressed the release of ANP. Rat CGRP showed similar effects but was approximately 300-fold more potent than amylin. Pretreatment with receptor antagonist for CGRP1 [rat alpha-CGRP (8-37)] or salmon calcitonin [acetyl-(Asn30, Tyr32)-calcitonin(8-32), (AC 187)] blocked the suppressive effect of ANP release and the positive inotropic effect by rat amylin. However, receptor antagonists for amylin [amylin (8-37), acetyl-amylin] did not block those effects. Amylin (8-37), acetyl-amylin, or rat alpha-CGRP (8-37) alone accentuated the release of ANP with no changes in atrial contractility. The effect of rat amylin and rat amylin (8-37) on the ANP release was attenuated in streptozotocin-treated rats. We suggest that amylin suppressed ANP release with increased atrial contractility through receptors for CGRP1 and salmon calcitonin and the attenuation of amylin and its antagonist on ANP release from streptozotocin-treated rat atria may be due to the downregulation of amylin receptor.
Piao
Feng Lian
FL
Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, 2-20 Keum-Am-Dong-San, Jeonju 561-180, South Korea.
Cao
Chunhua
C
Han
Jeong Hee
JH
Kim
Sung Zoo
SZ
Cho
Kyung Woo
KW
Kim
Suhn Hee
SH
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D001794:Blood Pressure; D002116:Calcitonin / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D015536:Down-Regulation; D058228:Islet Amyloid Polypeptide; D008297:Male; D011674:Pulse; D051381:Rats; D018003:Receptors, Calcitonin / Q000037:antagonists & inhibitors / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*
D000682:Amyloid; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D058228:Islet Amyloid Polypeptide; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; C028815:salmon calcitonin; D009320:Atrial Natriuretic Factor; D002116:Calcitonin