Rod outer segment membrane guanylate cyclase type 1-linked stimulatory andinhibitory calcium signaling systems in the pineal gland: Biochemical, molecular, and immunohistochemical evidence

Recent evidence indicates the presence of a novel alpha(2D/A)-adrenergic re ceptor (alpha(2D/A)-AR) linked membrane guanylate cyclase signal transducti on system in the pineal gland. This system operates via a Ca2+-driven rod o uter segment membrane guanylate cyclase (ROS-GC). In the present study, thi s transduction system has been characterized via molecular, immunohistochem ical, and biochemical approaches. The two main components of the system are ROS-GC1 and its Ca2+ regulator, S100B. Both components coexist in pinealoc ytes where the signaling component alpha(2D/A)-AR also resides. The presenc e of ROS-GC2 was not detected in the pineal gland. Thus, transduction compo nents involved in processing alpha(2D/A)-AR-mediated signals are Ca2+, S100 B, and ROS-GC1. During this investigation, an intriguing observation was ma de. In certain pinealocytes, ROS-GC1 coexisted with its other Ca2+ modulato r, guanylate cyclase activating protein type 1 (GCAP1). In these pinealocyt es, S100B was not present. The other GCAP protein, GCAP2, which is also a k nown modulator of ROS-GC in photoreceptors, was not present in the pineal g land. The results establish the identity of an alpha(2D/A)-AR-linked ROS-GC 1 transduction system in pinealocytes. Furthermore, the findings show that ROS-GC1, in a separate subpopulation of pinealocytes, is associated with an opposite Ca2+ signaling pathway, which is similar to phototransduction in retina. Thus, like photoreceptors, pinealocytes sense both positive and neg ative Ca2+ signals, where ROS-GC1 plays a pivotal role; however, unlike pho toreceptors, the pinealocyte is devoid of the ROS-GC2/GCAP2 signal transduc tion system.