Gilman , Alfred Goodman

(1941––sp;–sp;) American pharmacologist

The son of Alfred Gilman Snr, a noted pharmacologist, Gilman received his PhD from Case Western Reserve University, Cleveland, Ohio, in 1969. After working at the University of Virginia Medical School from 1971 until 1981, Gilman moved to the University of Texas Southwestern Medical Centre, Dallas, where he became professor of pharmacology.

Gilman's work has been on the processes by which hormones, neurotransmitters, and other stimuli – the so-called ‘first messengers’ – influence cellular activity. It had been shown by Earl Sutherland in 1971 that hormones do not actually enter cells. They seem to bind to receptor sites on the cell's surface and then produce a “second messenger,” cAMP (cyclic adenosine monophosphate), which initiates the appropriate cellular response.

It was further shown by Martin Rodbell that other factors, namely, an amplifier and a transducer, were required in the process. Rodbell identified the enzyme adenylate cyclase (AC) as the amplifier and demonstrated that transducers would only work in the presence of the energy-rich molecule guanine triphosphate (GTP).

Gilman set out to elucidate the process further. He established in the late 1970s that the transducers were in fact proteins. They were initially named ‘guanine nucleotide binding proteins’, a term quickly shortened to G proteins. Gilman went on to outline the main steps in cellular signaling as:

1. A hormone, neurotransmitter, etc., binds to a cell receptor.

2. The receptor binds to and activates a G protein.

3. The activated G protein binds to GTP.

4. The activated GTP stimulates AC to produce cAMP.

5. cAMP produces an appropriate cellular response.

G proteins have been shown to play a number of important physiological roles. In cholera, for example, a toxin is produced that freezes G proteins into their GTP-bound activated state, producing in the body a massive fluid loss with consequent dehydration. G proteins are also thought to be involved in some aspects of diabetes and some types of cancer.

Gilman shared the 1994 Nobel Prize for physiology or medicine with Martin Rodbell for their work on G proteins.