Intracellular second messengers involved in melatonin signal transduction in chicken splenocytes in vitro

Abstract

The pineal hormone melatonin exhibits immunomodulatory activity well documented in mammals and birds. The mechanism of melatonin action within the immune system is, however, poorly understood. In mammalian immune cells in vitro, melatonin acts mainly as an antiapoptotic, oncostatic and antiproliferative agent, and these effects are exerted via specific receptors or are related to its free radical scavenging activity. In previous studies we have found that in short-term chicken splenocyte cultures in vitro melatonin stimulated basil proliferation and inhibited that stimulated with phytohemagglutinin, a T-cell mitogen. This paper is devoted to the involvement of membrane receptors, previously characterised by us as MT2 (Mel(1b)) and Mel(1c) subtypes, in the above mentioned melatonin effects in chicken splenocyte cultures. For this purpose, in present study a nonselective melatonin receptor antagonist, luzindole, and the selective MT2 blocker, 4P-PDOT, were used. The effect of melatonin on second messengers, cyclic adenosine-3',5'-monophosphate (cAMP) and inositol-1,4,5-trisphosphate (IP(3)), involved in the regulation of proliferation, was examined. We have found that the stimulation of proliferation occurs via Mel(1c) receptor and is associated with the changes in intracellular second messengers concentration: a decrease in cAMP and an increase in IP(3). In contrast, in mitogen-activated splenocytes, melatonin-induced inhibition of proliferation is mediated by MT2 receptors and is related to cAMP accumulation, as well as a decrease in IP(3). In conclusion, we have demonstrated that the stimulatory and inhibitory effect of melatonin on chicken splenocytes in vitro, dependent on the magnitude of cell stimulation, resulted from two different subtypes of membrane receptors.

Diurnal differences in melatonin effect on intracellular Ca2+ concentration in chicken spleen leukocytes in vitro

“…Our long‐term goal is to understand the physiological mechanism(s) of the action of melatonin on the chicken immune system. Previously, we demonstrated that, in chicken splenocyte cultures, melatonin stimulates proliferation, most probably through the activation of the Mel 1c receptor [21]. In the present study, we examined day/night differences in the expression of all three subtypes of membrane‐located melatonin receptors in chicken lymphoid organs and in splenocytes cultured for 30 hr.…”

Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway

“…Moreover, through the dissociation of βγ subunits of Gi, melatonin activates MAP kinases as well as the Ras-MEK pathway to stimulate ERK phosphorylation (Carbajo-Pescador et al, 2011[8]; Pearson et al, 2001[42]; Witt-Enderby et al, 2003[60]). Activation of the MT2 can also result in decreases in cGMP, decreases cAMP formation and PI hydrolysis via Gαi subunit activation (Dubocovich et al, 2010[16]; Markowska et al, 2004[37]). Melatonin acted through MT1 and MT2 receptors to activate hypothalamic Akt/PKB and protein kinase B to suppress hepatic gluconeogenesis in rats (Faria et al, 2013[20]).…”

Short‐ and long‐term effects of melatonin on myocardial post‐ischemic recovery

“…obs.). Other intracellular second messengers are inositol trisphosphate in splenocytes [35] and IRS‐1/PI‐3‐kinase in the hypothalamus [36], the significance of which remains to be established.…”