Nitric oxide is formed in a subpopulation of rat pineal cells and acts as an intercellular messenger

In the rat pineal, formation of the second messenger cyclic GMP (cGMP) is under adrenergic control. Two important sequential steps mediate adrenergic signal transduction by cGMP, receptor-stimulated nitric oxide (NO) formation by the enzyme NO synthase I (NOS I), and NO-induced cGMP formation by the cytosolic enzyme guanylyl cyclase. With regard to the first step in cGMP transduction (i.e. NO formation) we found, by means of NOS I immunostaining and NADPH-diaphorase staining, that the presence of NOS I was restricted to a subpopulation of pineal cells, generally surrounded by NOS I-negative cells. Considering the fact that NO is able to permeate the cell membrane, the question arises whether the second step in cGMP signalling (i.e. NO-induced cGMP formation) is restricted to the NO-forming cell itself or takes place in neighboring cells as well. It was found that oxyhemoglobin, which scavenges NO but does not enter cells, strongly decreased adrenergic cGMP response. This suggests that a considerable part of adrenergically induced NO stimulates cGMP formation in neighboring cells. Our findings indicate that in the rat pineal the components of adrenergic cGMP transduction are largely distributed among two types of cells: NOS I-containing pineal cells where adrenoceptor stimulation induces NO formation, and neighboring cells in which NO stimulates cGMP formation.