Beta A4(25-35) modulates substance P effect on @entity35 skin microvasculature in aged XXXX : pharmacological manipulation using SEC-receptor ligands.

@entity32 @entity10133 @entity535 @entity2359 @entity195 @entity35 @entity13624 @entity4655 @entity4756
The primary constituent of the senile plaque core in @entity195 ( @entity195 ) is the beta-amyloid protein (beta A4). A discrete 11 @entity535 fragment of the beta A4, beta A4(25-35), has been implicated in mediating in vitro @entity2359 and an inflammatory response surrounding senile plaques in @entity195 via interaction with the Serpin Enzyme Complex (SEC) receptor. Substance @entity10133 ), a neuropeptide of the @entity4756 family and a major mediator of @entity13624 , shows sequence homology to beta A4(25-35) and has been shown to protect against the @entity2359 of beta-amyloid. SP also competes with beta A4(25-35) for binding to the SEC-receptor. SP neurons have also been found to be depleted in @entity195 . Using a blister model of @entity32 in the @entity35 hind footpad, we have examined the effect of beta A4(25-35) and its interaction with SP in @entity35 skin microvasculature and determined age-related changes to these phenomena. In addition, pharmacological manipulation of these responses using SEC-receptor ligands (peptide 105Y and 105C) was also undertaken. Because of the evidence for co-existence and co-release of SP and @entity4655 ( @entity4655 ) from the peripheral terminals of sensory nerves, it was of interest to examine the interaction of @entity4655 with beta A4(25-35) on @entity35 skin microvasculature. beta A4(25-35) (10 microM) was perfused over the base of a blister raised on the hind footpad of anaesthetised young and old @entity35 . This was followed by perfusion of SP (1 microM) or @entity4655 (1 microM) after Ringer's solution. Relative blood flow was monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)
