A chemical within a cell that is responsible for initiating the response to a signal from a chemical messenger (such as a hormone, neurotransmitter, or growth factor) that cannot enter the target cell itself, for example because it is not lipid-soluble and is therefore unable to cross the plasma membrane. A common second messenger is cyclic AMP; the signal for its formation within the cell by the enzyme adenylate cyclase is transmitted from hormone receptors on the cell surface by a G protein. Inositol 1,4,5-trisphosphate (see inositol), diacylglycerol, calcium ions, and nitric oxide are other examples of second messengers.