increase CO production, followed by the stimulation of soluble guanylyl cyclase/cyclic GMP vasorelax- ation pathway.
5. Future Prospects
So far, there are many reports regarding peptide - functionality (Hartmann and Meisel 2007 ). Some peptides showed vasorelaxation, antioxidative nitrogen of PAA to Glu from domains III and IV is
essential in eliciting effective Ca 2+ channel blocking action. This indicates that an ionization of nitrogen of PAA would be important for blocking action at the intracellular channel site. The reported pKa of verapamil was around 8.8, indicating that an ionized form of verapamil is dominant at the physiological condition (pH 7.4). According to this structural information on PAA - type blockers, the developed Ca 2+ channel blocking action of Trp - His might be associated with its structural similarity with PAA.
In a recent peptide - induced vasorelaxation study (Erdmann et al. 2006 ), it was found that Met - Tyr
ACh ACh
Wash KCl PE
PE 0.51.0 2.0
3.0 3.5
4.0 5.0 Wash
Kovacs - Nolan 2006 ; Meisel 2005 ; Horiguchi et al.
2005 ). Given these diverse functionalities and the present fi ndings on antihypertensive actions, the intake of peptides would be of benefi t for maintaining our homeostasis, and further studies should be per- formed to overwhelm any discrepancy between in vitro and in vivo phenomena of bioactive peptides.
(Erdmann et al. 2006 ; Zhu et al. 2006 ; Hernandez - Ledesma et al. 2005 ), antithrombotic (Chabance et al.
1995 ), and hypocholesterolemic effects (Nagaoka et al. 2001 ; Morikawa et al. 2007 ); and others showed mineral binding, (Walker et al. 2006 ) as well as antimicrobial (McCann et al. 2006 ) and immuno- modulatory effects (Takahashi et al. 1994 ; Mine and
Figure 4.6. Schematic representation of Trp - His binding site to a voltage - gated L - type Ca 2+ channel in VSMC. Vasorelaxation profi le of Trp - His in the presence ( 䊐 ) or absence ( 䊏 ) of nifedipine (2.5 nmol/L) or verapamil (30 nmol/L).
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