Pharmacological profiling of neuropeptides on rabbit vaginal wall and vaginal artery smooth muscle in vitro.
OBJECTIVE
Hypothalamic neuropeptides centrally modulate sexual arousal. However, the role of neuropeptides in peripheral arousal has been ignored. Vascular and non-vascular smooth muscle relaxation in the vagina is important for female sexual arousal. To date, in vitro studies have focused on vaginal strips with no studies on vaginal arteries. The aim of this study was to compare the effects of sexual hypothalamic neuropeptides on rabbit vaginal wall strips and arteries.


METHODS
Tissue bath and wire myography techniques were used to measure isometric tension from strips and arteries, respectively.


RESULTS
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) relaxed both preparations, effects that were only antagonized by the VIP/PACAP antagonist VIP6-28 (10 nM) and the PAC(1) antagonist PACAP 6-38 (1 microM). The melanocortin agonist alpha-melanocortin-stimulating hormone (1 microM), but not bremelanotide (1 microM), also relaxed both preparations. Oxytocin and vasopressin contracted vaginal preparations, which could be antagonized by the V(1A) antagonist SR 49059. Neuropeptide Y (NPY) and the NPY Y(1) agonist Leu(31), Pro(34) NPY only contracted arteries, which was antagonized by the NPY Y(1) receptor antagonist BIBP 3226. Melanin-concentrating hormone (MCH; 1 microM) contracted arteries.


CONCLUSIONS
Hypothalamic neuropeptides can exert contractile and relaxant effects on vaginal strips and arteries. NPY Y(1), V(1A), MCH(1) antagonists as well as VIP/PAC(1) agonists may have therapeutic potential in both central and peripheral female sexual arousal. Differences in effect of neuropeptides between preparations raise the question of which preparation is important for female sexual arousal.
Aughton
K L
KL
Discovery Biology, Pfizer Global Research & Development, Sandwich, UK.
Hamilton-Smith
K
K
Gupta
J
J
Morton
J S
JS
Wayman
C P
CP
Jackson
V M
VM
D000818:Animals; D005260:Female; D008958:Models, Molecular; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D014621:Vagina / Q000033:anatomy & histology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009478:Neuropeptide Y; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide