A second look at the second messenger hypothesis

Several hundred hormones, neurotransmitters, growth factors and other "first messengers" bind to specific cell membrane receptors and induce a myriad of effects: short term, transport, metabolic, mitotic and regulation of thousands of specific genes. Yet, less than a dozen "second messengers" have been clearly established to date. Even allowing for the discovery of a large number of additional second messengers, there remains a paradox in terms of information-transfer within the cell: how can so many specific signals produce so many effects through so few relatively nonspecific intermediates? We consider several possible solutions to this paradox, including the hypothesis that signal specificity is encoded in part in the primary structure of the receptor.