Bombesin receptor antagonists. 2. Analogues based on substance P antagonists.
Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour).
Rusconi
L
L
Ricerca & Sviluppo Farmitalia Carlo Erba S.r.l.-Erbamont Group, Milano, Italia.
de Castiglione
R
R
Gozzini
L
L
Ciomei
M
M
Molinari
I
I
Basilico
L
L
Rubino
T
T
Vinayek
R
R
Gardner
J D
JD
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism; D000818:Animals; D006120:Grooming / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000037:antagonists & inhibitors*; D001743:Urinary Bladder / Q000187:drug effects
D008934:Mitogens; D018004:Receptors, Bombesin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D000681:Amylases