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Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale, Unité 317, 31073 Toulouse Cedex, France
We have recently demonstrated that
natriuretic peptides (NPs), which are known for regulation of blood
pressure via membrane guanylyl cyclase (GC) receptors, are lipolytic in
human adipose tissue. In this study, we compared the NP control of
lipolysis in adipocytes from humans, nonhuman primates (macaques),
rodents (rats, mice, hamsters), and nonrodent mammals (rabbits, dogs). Isolated adipocytes from these species were exposed to increasing concentrations of atrial NP (ANP) or isoproterenol (
-adrenergic agonist). Although isoproterenol was lipolytic in all of the species, ANP only enhanced lipolysis in human and macaque adipocytes. In primate fat cells, NP-induced lipolysis involved a cGMP-dependent pathway. Binding studies and real-time quantitative PCR assays revealed
that rat adipocytes expressed a higher density of NP receptors compared
with humans but with a different subtype pattern of expression; type-A
GC receptors predominate in human fat cells. This was also confirmed by
the weak GC-activity stimulation and the reduced cGMP formation under
ANP exposure in rat adipocytes compared with human fat cells. In
conclusion, NP-induced lipolysis is a primate specificity, and
adipocytes from ANP-nonresponsive species present a predominance of
"clearance" receptors and very low expression of "biologically
active" receptors.
guanylyl cyclase; receptor subtypes; adipose tissue; cGMP
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