Receptor Pharmacology

Novel neuropeptides and control of neurotransmission

This is a collaborative study with Dr. J Bowie of the Department of Chemistry.

The frog neuropeptide caerulein resembles the mammalian neuropeptide cholecystokinin 8. However, frogs also secrete variants of these peptides at different stages of their life cycle (R.V.Baudinette, P. Boontheung and J.H.Bowie - unpublished observations). The function of these variant peptides is not known, although there is some suggestion that these may have selectivity for different forms of the mammalian receptors for cholecystokinin.Both caerulein and cholecystokinin 8 act on the mammalian hormone receptors for cholecystokinin on smooth muscle and reduce blood pressure at nanomolar concentrations. Caerulein is also a powerful analgesic, and a modulator of immune function. Some of these variant peptides may be more specific for the immune function actions over the blood pressure response.

Dr. Bowies group have recently isolated and characterised a number of new peptides from frogs that are related the amphibian neuropeptide caerulein, this in turn is related to the mammalian neuropeptide cholecystokinin:-

Caerulein		pGlu Gln Asp Tyr (SO3) Thr Gly Trp Met Asp Phe-NH2
Cholecystokinin 8		 Asp Tyr (SO3) Thr Gly Trp Met Asp Phe-NH2

Dr. Bowie has synthesised a number of these peptides .This study will determine if these variant peptides are indeed more specialized than the parent peptide. Thus this study is of importance for understanding the fundamental biology of frogs, but may have wider implications for mammalian and human biology, and provide clues to the development of new drugs.