The molluscan cardioexcitatory peptide FMRFamide (Phe-Met- Arg-Phe-NH2), together with four structurally similar peptides, constitute a closely related nuclear family which now includes among its membership two tetrapeptides and three heptapeptides. The tetra-and heptapeptides have different phyletic distributions among the molluscs, and have distinctive effects and receptors on muscles and nerves. Antisera to FMRFamide also cross-react widely with antigens in the nerve and endocrine cells of non- molluscan groups, both vertebrate and invertebrate. Some of this immunoreactivity is due to established peptides, but previously unknown peptides have also been discovered. These immunochemical results are manifestations of a large, heterogeneous, widespread, extended peptide family; it is characterized by an amidated C-terminal dipeptide of the form Arg-X-NH2 (where X is an aromatic residue). The first long-term goal of this project is to examine the tissue distributions, actions and physiological roles of the individual FMRFamide-related peptides (FaRPs) making up the model nuclear family in the pulmonate snail, Helix aspersa. The receptors complementary to the FaRPs will be characterized by studying the structure- activity relations (SAR) of these peptides on whole tissues, biochemical mechanisms, and radioligand-receptor binding properties. The variation in the levels and potency of the FaRPs, as a function of the activity state of the snails will also be examined. The second long-term goal is to determine the phyletic distribution, size, and limits of the extended family of FaRPs, and to define its relationship with the nuclear family in molluscs. New extra-molluscan FaRPs will be sought in central nervous extracts of vertebrates and key invertebrates. The effects, of both the nuclear and extended FaRPs, on vertebrate vascular smooth muscle will be tested and the receptors characterized by SAR. The relationship between the nuclear family of FaRPs and the extended family may reside in the homology of their receptors; the similarities between the peptides themselves are probably due to convergence.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL028440-07
Application #
3485932
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1981-06-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Organized Research Units
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Gainey Jr, L F; Vining, K J; Doble, K E et al. (1999) An endogenous SCP-related peptide modulates ciliary beating in the gills of a venerid clam, Mercenaria mercenaria. Biol Bull 197:159-73
Khan, H R; Price, D A; Doble, K E et al. (1998) FMRFamide-related peptides, partial serotonin depletion, and osmoregulation in Helisoma duryi (Mollusca: Pulmonata). J Comp Neurol 393:25-33
Reich, G; Doble, K E; Price, D A et al. (1997) Effects of cardioactive peptides on myocardial cAMP levels in the snail Helix aspersa. Peptides 18:355-60
Greenberg, M J; Doble, K E; Lesser, W et al. (1997) Characterization of myomodulin-related peptides from the pulmonate snail Helix aspersa. Peptides 18:1099-106
Reich, G; Doble, K E; Greenberg, M J (1997) Protein phosphorylation in snail cardiocytes stimulated with molluscan peptide SCPb. Peptides 18:1311-4
Price, D A; Doble, K E; Lesser, W et al. (1996) The peptide pQFYRFamide is encoded on the FMRFamide precursor of the snail Helix aspersa but does not activate the FMRFamide-gated sodium current. Biol Bull 191:341-52
Groome, J R; Townley, M A; Watson 3rd, W H (1994) Excitatory actions of FMRFamide-related peptides (FaRPs) on the neurogenic Limulus heart. Biol Bull 186:309-18
Cottrell, G A; Lutz, E M; Price, D A et al. (1994) N-terminally extended FMRFamide-related peptides of Helix aspersa: processing of the precursor protein and distribution of the released peptides. Mol Cell Neurosci 5:632-41
Madrid, K P; Price, D A; Greenberg, M J et al. (1994) FMRFamide-related peptides from the kidney of the snail, Helisoma trivolvis. Peptides 15:31-6
Chin, G J; Payza, K; Price, D A et al. (1994) Characterization and solubilization of the FMRFamide receptor of squid. Biol Bull 187:185-99

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