A novel physiological property of snake bradykinin-potentiating peptides-reversion of MK-801 inhibition of nicotinic acetylcholine receptors.
The first naturally occurring angiotensin-converting enzyme (ACE) inhibitors described are pyroglutamyl proline-rich oligopeptides, found in the venom of the viper Bothrops jararaca, and named as bradykinin-potentiating peptides (BPPs). Biochemical and pharmacological properties of these peptides were essential for the development of Captopril, the first active site-directed inhibitor of ACE, currently used for the treatment of human hypertension. However, a number of data have suggested that the pharmacological activity of BPPs could not only be explained by their inhibitory action on enzymatic activity of somatic ACE. In fact, we showed recently that the strong and long-lasting anti-hypertensive effect of BPP-10c [<ENWPHPQIPP] is independent of somatic ACE inhibition. On the other hand, nicotinic acetylcholine receptors expressed in blood vessels have been related to blood pressure regulation. Therefore, we have studied the effects of BPP-10c on acetylcholine receptor function in the PC12 pheochromocytoma cell line, which following induction to neuronal differentiation expresses most of the nicotinic receptor subtypes. BPP-10c did not induce receptor-mediated ion flux, nor potentiated carbamoylcholine-provoked receptor activity as determined by whole-cell recording. This peptide, however, alleviated MK-801-induced inhibition of nicotinic acetylcholine receptor activity. Although more data are needed for understanding the mechanism of the BPP-10c effect on nicotinic receptor activity and its relationship with the anti-hypertensive activity, this work reveals possible therapeutic applications for BPP-10c in establishing normal acetylcholine receptor activity.
Nery
Arthur A
AA
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CEP 05508-900, São Paulo, SP, Brazil.
Trujillo
Cleber A
CA
Lameu
Claudiana
C
Konno
Katsuhiro
K
Oliveira
Vitor
V
Camargo
Antonio C M
AC
Ulrich
Henning
H
Hayashi
Mirian A F
MA
D000818:Animals; D017837:Bothrops; D001920:Bradykinin / Q000378:metabolism*; D002217:Carbachol / Q000378:metabolism; D018679:Cholinergic Agonists / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D006801:Humans; D018733:Nicotinic Antagonists / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
D018679:Cholinergic Agonists; D003435:Crotalid Venoms; D018733:Nicotinic Antagonists; D010455:Peptides; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D016291:Dizocilpine Maleate; D002217:Carbachol; D001920:Bradykinin