Effects of neuropeptide Y and agonists selective for neuropeptide Y receptor sub‐types on arterioles of the guinea‐pig small intestine and the rat brain

Abstract

1 The actions of neuropeptide Y (NPY) and agonists selective for NPY receptor subtypes were examined on arterioles from the guinea-pig small intestine and the rat pia in order to characterize the receptors mediating the vasoconstrictor and potentiating effects of NPY. 2 A method was developed for measuring the potentiating effects of NPY in situations where it was not possible to obtain a full concentration-response relationship for the vasoconstrictor. NPY, 50 nM, had a greater potentiating effect on the guinea-pig intestinal arterioles than those from the rat pia.

Interactions between neuropeptide Y and the adenylate cyclase pathway in rat mesenteric small arteries: role of membrane potential

“…This may explain the potentiating effect of the peptide, since slight depolarizations caused either by raising extracellular K¤ (Mulvany et al 1982) or by denervation (Neild, 1987) are known to increase the sensitivity of arterial smooth muscle to several vasoconstrictors. NPY has been shown earlier to elicit depolarization in brain large arteries (Abel & Han, 1989) and pial arterioles (Xia, Neild & Kotecha, 1992) and in rat caudal artery (Neild, 1987). In these studies, as in the present experiments, the effects of the peptide on membrane potential were slow in onset and sustained, and NPY also caused a weak contraction but potentiated the vasoconstriction elicited by other agonists.…”

Reduction of vasoconstriction mediated by neuropeptide Y Y2 receptors in arterioles of the guinea‐pig small intestine

“…The Y2-selective agonists, PYY-(13-36) (Wahlestedt & Hakanson, 1986) or N-acetyl[Leu28,Leu3`]NPY-(24-36) (Potter et al, 1994) in the same concentration (50 nM) significantly decreased the response. Representative traces are shown in Figure 1, and quantitation of the potentiation is summarised in Table 1. Discussion These experiments show that arterioles of the guinea-pig intestinal submucosa express NPY Y2 receptors in addition to the Yj receptors described previously (Xia et al, 1992). These Y2 receptors mediate a reduction of the constriction caused by high K+, a constriction that is due entirely to depolarization of the smooth muscle and subsequent entry of Ca21 through depolarization-activated channels.…”

“…These Y2 receptors mediate a reduction of the constriction caused by high K+, a constriction that is due entirely to depolarization of the smooth muscle and subsequent entry of Ca21 through depolarization-activated channels. We have previously shown that responses to noradrenaline, which rely mainly on Ca2+ release from the internal stores, are not affected by one of the Y2-selective agonists used here, PYY-(13-36) (Xia et al, 1992). We therefore suggest that there are Y2 receptors on the smooth muscle which modulate the opening of voltage-sensitive Ca2+ channels, as they do in nerve terminals (Foucart et al, 1993).…”

“…This action is mediated by the Y1 subtype of NPY receptor (Xia et al, 1992). Another receptor, the Y2 receptor, has been found on nerve terminals where it reduces neurotransmitter release (Potter, 1987), probably by a reduction of Ca2" influx through voltage-sensitive Ca21 channels (Foucart et al, 1993).…”

“…High potassium solution was made by replacing 95 mmol 1-1 of NaCl with KC1, to give a final K+ concentration of 100 mM. It was applied to the arteriole by pressure ejection from a micropipette using pulses 100-400 ms in duration, or in the superfusing solution to determine the maximum constriction for the arteriole (Neild & Kotecha, 1989 The potentiating effect of NPY was calculated using an index P (Xia et al, 1992) defined as:…”