Effects of amylin and salmon calcitonin on beta-endorphin-induced growth hormone and prolactin secretion in the rat.
In this study we examined the possible interplay of amylin (AMY) and salmon calcitonin (sCT) in the central control of growth hormone (GH) and prolactin (PRL) secretion in male rats. For this purpose we first compared effects of central intracerebroventricular (i.c.v.) admininstration of various doses of AMY (2.5-2,500 ng/rat) and sCT (2.2-220 ng/rat) on beta-endorphin (beta-END, 0.5 microg/rat)-induced GH and PRL secretion. AMY and sCT dose-dependently inhibited beta-END-induced GH secretion, whereas only sCT was able to inhibit beta-END-induced PRL secretion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY8-37, 2. 5 microg/rat, i.c.v.). AMY8-37 significantly enhanced the GH-stimulatory action of beta-END. AMY8-37, administered prior to AMY and sCT, significantly removed the inhibitory effect of both AMY and sCT on beta-END-induced GH release, suggesting that both peptides mediate their response on GH through a common receptor. In vitro competition binding studies on rat hypothalamic membranes have shown that both AMY and sCT compete with [125I]rAMY binding with half inhibition (IC50) values of 3.6 x 10(-11) and 1.6 x 10(-10) M, respectively. Binding of [125I]sCT was inhibited by sCT with an IC50 of 1.09 x 10(-10) M and to a lesser extent by AMY with an IC50 of 1. 3 x 10(-6) M. Thus it is possible that the two peptides recognize a common hypothalamic receptor but with different affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL-releasing activity of beta-END indicates that different receptor subtypes for sCT are involved in the endocrine effects of sCT and only those mediating the modulatory action of GH respond to AMY.
Pagani
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F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy. Francesca.Pagani@unimi.it
Netti
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C
Guidobono
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F
Lattuada
N
N
Ticozzi
C
C
Sibilia
V
V
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D058228:Islet Amyloid Polypeptide; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001615:beta-Endorphin / Q000494:pharmacology*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C109255:amylin (8-37); D001615:beta-Endorphin; C028815:salmon calcitonin; D011388:Prolactin; D013006:Growth Hormone; D002116:Calcitonin