Periodate-induced increase in cyclic GMP in mouse and guinea pig splenic cells in association with mitogenesis

Abstract

INTERACTION of the lectins phytohaemagglutinin (PHA) and concanavalin A (con A) with the lymphocyte plasma membrane initiates a sequence of metabolic events leading to cell proliferation. The numerous alterations in cellular components and processes that occur early after mitogenic stimulation include enhanced uptake of nucleotides², amino acids^3,4, sugars⁵, Ca²⁺ (ref. 6), and K⁺ (ref. 7), enhanced activity of several membrane enzymes^8,9, accelerated turnover of phospholipids^10,11, increased membrane fluidity¹² and an increased accumulation of cellular cyclic 3′, 5′-guanosine monophosphate (cyclic GMP)^13–15. Demonstrations that exogenous cyclic GMP can stimulate definable functions in lymphocytes^16,17, including proliferation¹⁸, and that there is an association between phytomitogen action and cyclic GMP accumulation suggest that this nucleotide is a positive effector of proliferation. To investigate further how cyclic GMP may be involved in this sequence of events, we have studied the effects that the oxidant periodate (IO₄) and the reducing agent cysteine have on the cyclic nucleotide levels of rodent splenic cells¹. IO₄ stimulates lymphocyte proliferation¹⁹ and because the oxidant produces definable chemical alterations in membrane components, which can be prevented by reducing agents²⁰, studies with these agents may provide insights into the regulation of cyclic GMP metabolism in relation to mitogenic stimulation.