The vasorelaxant effect of pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide in isolated rat basilar arteries is partially mediated by activation of nitrergic neurons.
The structurally related neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are recognised by two G protein-coupled receptors, termed VPAC(1)-R and VPAC(2)-R, with equal affinity. PACAP and VIP have previously been shown to relax cerebral arteries in an endothelium-independent manner. The aim of the present study was to test if intramural neurons are involved in the mediation of PACAP/VIP-induced vasodilatory responses. Therefore, the vascular tone of isolated rat basilar arteries was measured by means of a myograph. The vasorelaxing effect of PACAP was assessed in arteries precontracted by serotonin in the absence or presence of different test compounds known to selectively inhibit certain signaling proteins. The vasorelaxant effect of PACAP could be significantly reduced by the inhibitor of neuronal N-type calcium channels omega-conotoxin GVIA (omega-CgTx), as well as by 3-bromo-7-nitroindazole (3Br-7-Ni), an inhibitor of the neuronal nitric oxide-synthase (nNOS). The localization of N-type calcium channels and VPAC-Rs within the rat basilar artery was investigated by confocal laser scanning microscopy using omega-CgTx- and VIP-analogs labelled with fluorescent dyes. These findings suggest that activation of intramural neurons may represent an important effector mechanism for mediation of the vasorelaxant PACAP-response.
Seebeck
Jörg
J
Department of Pharmacology, Christian-Albrechts-University (CAU) Kiel, Hospitalstr. 4, D-24105, Kiel, Germany. jseebeck@pharmakologie.uni-kiel.de
Löwe
Marcus
M
Kruse
Marie Luise
ML
Schmidt
Wolfgang E
WE
Mehdorn
H Maximilian
HM
Ziegler
Albrecht
A
Hempelmann
Ralf G
RG
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D009479:Neuropeptides / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D020960:omega-Conotoxins / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D020864:Calcium Channels, N-Type; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020960:omega-Conotoxins; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat