Browsing by Author "DONOSO, V"

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    ENDOTHELIN REDUCES MICROVASCULAR BLOOD-FLOW BY ACTING ON ARTERIOLES AND VENULES OF THE HAMSTER-CHEEK POUCH
    (1990) BORIC, MP; DONOSO, V; FOURNIER, A; STPIERRE, S; HUIDOBROTORO, JP
    Superfusion of the cheek pouch with 0.1-10 nM endothelin (E) produced a concentration-related reduction in the clearance of 22Na+ used as an indicator of microvascular plasma flow. The median effective concentration was about 2 nM. The time course of E action was also concentration related. Superfusion with 10 nM E for 10 min caused a greater than 80% reduction in 22Na+ clearance; the rate at which the action of E started was significantly faster than the rate at which its action ended. Recovery did not exceed 70% even though the tissue was superfused with drug-free buffer for 90 min. The E-induced reduction in 22Na+ clearance was associated with vasoconstriction, as determined by intravital microscopy. Arterioles by 4th branching order were more sensitive to E action than arterioles of 1st or 2nd order; however, the constriction lasted considerably longer in the latter vessels. E-induced venular constriction followed a pattern analogous to that of arterioles of the same category, with the exception that the finer venules responded the least. Pretreatment of the cheek pouch with 300 nM nifedipine diminished but did not abolish the 1 nM E-induced reduction in 22Na+ clearance, and the recovery of clerance upon E washout was not accelerated by nifedipine.
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    NEUROPEPTIDE-Y (NPY), AN ENDOGENOUS PRESYNAPTIC MODULATOR OF ADRENERGIC NEUROTRANSMISSION IN THE RAT VAS-DEFERENS - STRUCTURAL AND FUNCTIONAL-STUDIES
    (1988) DONOSO, V; SILVA, M; STPIERRE, S; HUIDOBROTORO, JP
    The role of neuropeptide tyrosine (NPY) on adrenergic neurotransmission was assessed in the rat vas deferens transmurally stimulated with square pulses of 0.15 or 15 Hz. Nanomoles of NPY inhibited the electrically-induced contractions on the prostatic half but not on the prostatic half but not on the epididymal end of the ductus. NPY was at least 200-fold more potent than norepinephrine or adenosine to produce an equivalent inhibition. Complete amino acid sequence of NPY is required for full agonist activity; deletion of tyrosine at the amino terminus, i.e., NPY fragment 2-36 was 3-fold less potent than the native peptide. NPY fragment 5-36, 11-36 or 25-36 were proportionally less potent than NPY. Avian pancreatic polypeptide was inactive. The presynaptic nature of the NPY acitivity was established measuring the outflow of 3H-norepinephrine from the adrenergic varicosities of the vas deferens electrically stimulated. In this assay, NPY was more potent than NPY 2-36 or NPY fragment 5-36. No inhibitory action of NPY was detected in K+ depolarized tissues. The inhibitory effect of NPY on the rat vas deferens neurotransmission was not significantly modified by yohimbine, theophylline or naloxone, indicating that the effect of NPY is not due to the activation of alpha2-adrenoceptors, adenosine receptors or opiate receptors respectively. Picrotoxin or apamin did not modify the inhibitory potency of NPY; verapamil or methoxyverapamil significantly reduced its potency. The inhibitory action of NPY is best explained through the activation of presynaptic NPY receptors that regulate norepinephrine release via a negative feedback mechanism. Structure activity studies give support to the notion of NPY receptors.