Peptidergic and adrenergic regulation of the intracellular 3′,5′-cyclic adenosine monophosphate content in cultured rat Schwann cells

Abstract

We investigated the role of neuropeptides and adrenergic agonists in the regulation of intracellular 3′,5′-cyclic adenosine monophosphate (cyclic AMP) contents in cultured Schwann cells from sciatic nerve of neonatal Sprague-Dawley rats. Of the neuropeptides examined, vasoactive intestinal polypeptide (VIP) and secretin markedly stimulated the accumulation of intracellular cyclic AMP in a time- and dose-dependent manner with half maximum at 3 and 12 min, and 2.8 × 10 −5 and 5.0 × 10 −5 M, respectively. While somatostatin, substance P, adrenocorticotropin (ACTH), β-endorphin, and nerve growth factor (NGF) did not show any effect on cyclic AMP metabolism, isoproterenol (IP), norepinephrine (NE) and epinephrine (E) also markedly elevated the Schwann cell cyclic AMP concentration. The rank-order of potency of these adrenergic catecholamines on cyclic AMP accumulation was isoproterenol > norepinephrine > epinephrine. Simultaneous addition of VIP or secretin to the Schwann cell culture synergistically enhanced the norepinephrine-induced elevation of intracellular cyclic AMP. The effect of norepinephrine was antagonized by a selective β 1-adrenergic antagonist but not by β 2- nor α-adrenergic antagonists. These results suggest that VIP, secretin, and β 1-adrenergic agonists alone or synergistically may play a part in the regulation of metabolism of Schwann cells mediated through a cyclic AMP-dependent mechanism.