Activity of centrally truncated analogues of neuropeptide Y at Y1 and Y2 receptor subtypes in vivo.
Neuropeptide Y (NPY), a sympathetic cotransmitter, has both prejunctional and postjunctional actions in the cardiovascular system. In anaesthetized rats, the bioassay system used here, NPY attenuates cardiac vagal action (a prejunctional or Y2 action) and increases blood pressure (a postjunctional or Y1 action). Several NPY analogues were tested against NPY. In these, centrally located amino acid sequences of various lengths were removed, and replaced with simpler 'spacers'. As the parent NPY molecule is considered to exist in a U-shape, these central truncations were intended to shorten the depth of the U, while maintaining the integrity of its two ends. The centrally truncated NPY analogues examined here retain activity at both receptor subtypes in vivo. These findings indicate that the U-shape of the parent molecule probably exists to assist stability, but that receptor binding occurs through sequences closer to the termini.
McCloskey
M J
MJ
Prince of Wales Medical Research Institute, Sydney, NSW, Australia.
Moriarty
M J
MJ
Tseng
A
A
Shine
J
J
Potter
E K
EK
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006321:Heart / Q000294:innervation; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D011921:Rats, Inbred WKY; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor