Role of adrenoceptor-coupled second messenger system in sympatho-adrenomedullary modulation of splenic macrophage functions in live fish Channa punctatus

In order to understand the role of sympatho-adrenomedullary (SAM) system in mediating stress effect on non-specific immune responses in fishes, the splenic macrophage phagocytic and respiratory burst activities of normal and chemically sympathectomized Channa punctatus under restraint stress were studied. Chemical sympathectomy abrogated the differential effects of acute stress on diverse functions of macrophages. The SAM regulation of macrophage activities was substantiated by in vitro experiments with catecholamines, the end product of SAM system. Further, for the first time in fishes, different adrenoceptors and their precise second messenger system regulating diverse functions of macrophages by catecholamines were demonstrated. Norepinephrine (NE)/epinephrine (E) decreased the phagocytosis through β-adrenergic receptor as only propranolol, the β-adrenergic receptor antagonist, blocked the suppressive effect of NE/E. However, dopamine (DA) regulates phagocytosis solely via the dopaminergic receptor. The DA effect was mimicked by DA receptor agonists, apomorphine and bromocryptine. Adenylate cyclase system linked to β-adrenoceptor/dopaminergic receptor seems to be involved in mediating the effect of catecholamine on phagocytosis since db cAMP inhibited the phagocytosis in a dose-dependent manner. In case of superoxide production, only phenoxybenzamine, an α-adrenergic receptor antagonist, was seen effective in blocking the stimulatory effect of NE/E. Further, Ca2+ as second messenger system coupled to α1-adrenergic receptor was shown to mediate this effect since phospholipase C (PLC) inhibitor, U73122 and intracellular calcium chelating agent, BAPTA-AM downregulated the NE/E-induced superoxide production. The role of calcium in modulation of superoxide production was also emphasized using calcium ionophore A23187.