Dear Dr.***

Your manuscript has been reviewed and

---- accepted for publication. A reprint order form will bc supplied by the Publisher,

---- XX is/herewith returned/not acceptable/for the following reasons:

---- not clear as checked in the manuscript.

---- the manuscript is too long.

---- sections of the manuscript which are noted (text, figures, tables) are not suitable for reproduction by photo-offset. Please resubmit it in accordance with the Information for Contributors.

Other Comments:

This has een reviewed by a biochemist specialized in hemopoiesis. As shown in his comments enclosed herewith, the specificity of Ca/CAMP effect is the major issue. When you can overcome these questions raised, the revised manuscript should be sent to the first Editor.

Reviewer's comment

General comment

1 . This manuscript describes that cAMP may be a second messenger inducing morphological changes in rat megakaryocytes. The authors reported that H-8, an inhibitor of cAMP-dependent protein kinase caused morphological changes in rat megaskaryocytes. They concluded that decrease in cellular CAMP Ievel induced morphological changes. I think that the change of cellular volume of megakaryocyte might be contributed to the explanation of decrease in cellular CAMP Ievel, and it seemed to be difticult to evaluate, howevr, they should have the direct evidence which shows the decrease of CAMP in megakaryocyies. They reported clearly that H-8 induced irregular villi- or filopodium-like changes, however, it is difticult to say it is specific for the action of cAMP-dependent pathway.

Specific comments

1 . In Figure I , not only thrombin but calcium ionophore stimulated 5-HT release from megakaryocytes. Do the authors have any data of H-8 on 5-HT release from megakaryocytes? Or do the authors have any report about it? The authors described that CAMP rather than calcium plays an important role in changing megakaryocyles. This phenomenon seems a new observation. When the authors can describe that CAMP is specific for the morphological changes of megakaryocytes rather than calcium and other protein kinases, this manuscript may be acoeptable, and the authors should answer to such a question.