Biomaterial Database

Structure-activity studies of RFamide analogues on central neurones of Helix aspersa. 1995

M L Chen, and R Sharma, and R J Walker

Department of Physiology and Pharmacology, University of Southampton, UK.

The effects of FMRFamide were compared with those of FMRFamide analogues, FLRFamide, LFRFamide, FFRFamide, LLRFamide, D-FMRFamide, F-D-MRFamide and FM-D-RFamide, and the fragments, MRFamide and LRFamide, on identified central neurones, F1, F2, F5 and E16, of the snail Helix aspersa, using intracellular recording and two electrode voltage clamp techniques. All FMRFamide analogues showed an inhibitory effect on F1 neurones with an order of potency: FLRFamide > FMRFamide > FFRFamide > LFRFamide >> LLRFamide. FMRFamide and FLRFamide exhibited a biphasic response on F2 neurones. At lower concentrations (< 10 microM), both peptides usually only excited while at higher concentrations (> 30 microM), exhibited an excitation followed by an inhibition. FFRFamide only excited F2 while LFRFamide and LLRFamide only inhibited F2. LRFamide and MRFamide (100 microM) were inactive on both F1 and F2. FLRFamide, LFRFamide, LLRFamide, FFRFamide and D-FMRFamide showed cross-interaction on the outward current induced by FMRFamide in F5. All peptides induced an outward current and also reduced the FMRFamide-induced current reversibly. In contrast, MRFamide, LRFamide and F-D-MRFamide failed to have direct effects on these neurones nor interact with the FMRFamide-induced current. We conclude that on F2 neurones Phe is essential for the activation of the RFamide receptor mediating the excitation and Met or Leu are important to activate the RFamide receptors mediating the inhibition. Removal of the N-terminal Phe, to give LRFamide and MRFamide render the peptides inactive. Therefore a tetrapeptide sequence is essential for the biological activity of FMRFamide analogues on these Helix neurones. FLRFamide, LFRFamide, LLRFamide, FFRFamide and D-FMRFamide exhibit a cross-interaction with FMRFamide. It is possible that these peptides also act on the same class of RFamide receptors as agonists to cause cross desensitization.

UI	MeSH Term	Description	Entries
D007447	Invertebrate Hormones	Hormones produced by invertebrates, usually insects, mollusks, annelids, and helminths.	Hormones, Invertebrate
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009479	Neuropeptides	Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.	Neuropeptide
D006372	Helix, Snails	A genus of chiefly Eurasian and African land snails including the principal edible snails as well as several pests of cultivated plants.	Helix (Snails),Snails Helix
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017952	Ganglia, Invertebrate	Clusters of neuronal cell bodies in invertebrates. Invertebrate ganglia may also contain neuronal processes and non-neuronal supporting cells. Many invertebrate ganglia are favorable subjects for research because they have small numbers of functional neuronal types which can be identified from one animal to another.	Invertebrate Ganglia,Ganglion, Invertebrate,Ganglions, Invertebrate,Invertebrate Ganglion,Invertebrate Ganglions
D018408	Patch-Clamp Techniques	An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.	Patch Clamp Technique,Patch-Clamp Technic,Patch-Clamp Technique,Voltage-Clamp Technic,Voltage-Clamp Technique,Voltage-Clamp Techniques,Whole-Cell Recording,Patch-Clamp Technics,Voltage-Clamp Technics,Clamp Technique, Patch,Clamp Techniques, Patch,Patch Clamp Technic,Patch Clamp Technics,Patch Clamp Techniques,Recording, Whole-Cell,Recordings, Whole-Cell,Technic, Patch-Clamp,Technic, Voltage-Clamp,Technics, Patch-Clamp,Technics, Voltage-Clamp,Technique, Patch Clamp,Technique, Patch-Clamp,Technique, Voltage-Clamp,Techniques, Patch Clamp,Techniques, Patch-Clamp,Techniques, Voltage-Clamp,Voltage Clamp Technic,Voltage Clamp Technics,Voltage Clamp Technique,Voltage Clamp Techniques,Whole Cell Recording,Whole-Cell Recordings
D019835	FMRFamide	A molluscan neuroactive peptide which induces a fast excitatory depolarizing response due to direct activation of amiloride-sensitive SODIUM CHANNELS. (From Nature 1995; 378(6558): 730-3)	FMRF,FMRF-NH2,FMRF-amide,FMRFamide, (D-Arg)-Isomer,FMRFamide, (D-Met)-Isomer,FMRFamide, (D-Phe)-Isomer,FMRFamide, (D-phenylalanine)-Isomer,Phe-Met-Arg-Phe-NH2,Phe-Met-Arg-Phe-amide,FMRF NH2,FMRF amide,Phe Met Arg Phe amide
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In