Prepro-Vasoactive Intestinal Polypeptide-Derived Peptide Sequences in Cerebral Blood Vessels of Rats: On the Functional Anatomy of Metabolic Autoregulation

Abstract

Summary: This study describes the distribution of pep tide sequences derived from the prepro-vasoactive intes tinal polypeptide (preproVIP) molecule in perivascular nerves of rat brain arteries and arterioles. The peptides were identified by immunohistochemistry using highly specific antibodies. Five peptide sequences (preproVIP 60-76, peptide histidine isoleucine (PHI), preproVIP 111-122, VIP, and preproVIP 15�170) were identified in the perivascular nerves throughout the arterial cerebral cir culation. The density of the immunoreactive fibers was highest in the nerves of the larger extracerebral arteries, declining in smaller branching arteries. All peptide se quences were identified in the nerves of small pial arte rioles overlying the cortical convexity, whereas capillar ies and veins contained no immunoreactive material. Rat vasoactive intestinal polypeptide (VIP) issynthesized from a precursor, preproVIP, consist ing of about 170 amino acid residues (Nishizawa et aI., 1985). PreproVIP can be divided functionally into six domains (Nishizawa et aI., 1985) that in clude the amino acid sequences of VIP and peptide histidine isoleucine (PHI), which are biologically active (e.g. Edvinsson and McCulloch, 1985). Other Abbreviations used: BA, basilar artery; ICA, inferior cerebel lar artery; PBS, potassium-phosphate-buffered saline; PBS-TX, PBS containing Triton X-IOO; PHI, peptide histidine isoleucine; SCA, superior cerebellar artery; VA, vertebral artery; VIP, va soactive intestinal polypeptide. 932Dendritic processes of neocortical neurons immunoreac tive for VIP and PHI could be followed towards the brain surface where the processes penetrated into the pial layer, often close to the pial vasculature. Some of the processes were also observed to enter the Virchow-Robin space, close to the arterioles. It is possible that cortical nerve cells containing VIP and PHI release the peptides in the perivascular space during periods of activity and thereby contribute to local vasodilatation associated with changes of neuronal function. Key Words: Vasoactive in testinal polypeptide (VIP)-Peptide histidine isoleucine VIP precursor-Immunohistochemistry-Radioimmuno assay-Cerebral blood vessels-Innervation-Rat Metabolic autoregulation.

Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging

“…It is also possible that vasodilator substances diffuse from active regions to adjacent nonactive regions or that the LFP is too small for some types of stimulation and target cells to become detected even with microelectrode techniques (Akgoren et al, 1996). Finally, neurons within the cortex and in subcortical structures project to cortical vessels, an arrangement that is fit to adjust flow to activity because the projections contain potent vasodilator substances (Zhang et al, 1991;Chedotal et al, 1994;Iadecola, 1998;Tong and Hamel, 2000;Vaucher et al, 2000). Thus, there are anatomical and physiological mechanisms that limit the physiological resolution, i.e., the accuracy of functional localization of the vascular signals in relation to the underlying neural signal, and the extent to which PET and fMRI studies can contribute to an exact localization of brain function.…”

Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.

“…Morphological, biochemical, and functional evidence indicates that vasoactive intestinal polypeptide (VIP) is a potent cerebrovascular vasodilator (1)(2)(3)(4)(5)(6). Although VIP causes vasodilation in vitro (7,8) and when applied locally to intracranial blood vessels (9), no consistent cerebrovascular effects could be demonstrated after systemic application of the peptide (10)(11)(12).…”

“…VIPa was first iodinated with Na'25I and Na127I (molar ratio of 125I/127I, 1:60) using a mild chloramine-T procedure (molar ratios of peptide/iodine/ chloramine T, 1:1:5). The HPLC-purified, iodinated VIPa was further characterized by enzymatic digestion with endoproteinase Lys-C, which cleaves VIPa at the single Lys15 residue, yielding peptide fragments [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] with 1251-bioVIPa (final concentration, 13.1 nM; 0.4 gCi/ml).…”

La physiologie de la circulation cérébrale

“…Cette vision a été modifiée depuis qu'il a été montré que des petites artères pie-mériennes reçoivent des afférences provenant du noyau du raphé dorsal (BONVENTO et al,. 1991) ou des neurones corticaux (ZHANG et al, 1991 …”