Generally,cell signal molecules are classified into the extracellular signal molecules (the first messengers) and the intracellular signal ones (the second messengers).Cyclic adenosine monophosphate (cAMP),calcium ions and calmodulin (CaM) are the traditional intracellular messengers,but they are also present in extracellular matrix (ECM).Some of them have been discovered to act as the first messengers through cell surface receptors.Other second messengers,such as cyclic guanosine monophosphate (cGMP),cyclic adenosine diphosphate ribose (cADPR) and annexin,are also found existing outside animal and plant cells.The existence of these messengers with intracellular-extracellular compatible functions in cells may be a regular biological phenomenon.These compatible messengers might be the communication factors between intracellular and extracellular regions or among the cell populations,and are also important in regulating cell development procedure.