Mechanism of "substance P": on mesenteric blood flow; interactions with opioid peptides.

The effects of close intra arterial injection of substance P (SP) and the interaction of SP with opioid peptides, have been studied on mesenteric blood flow in the anaesthetized dog. Injection of SP into the superior mesenteric artery caused a dose dependent increase in mesenteric blood flow. This effect was enhanced by pretreatment with the alpha 2 adrenergic antagonist yohimbine. The action of SP was significantly reduced by pretreatment with muscarinic and nicotinic cholinergic, dopamine and histamine (H1) receptor antagonists. Beta adrenergic, histamine (H2) and opiate receptor antagonists did not influence the action of SP. Pretreatment with tetrodotoxin partially inhibited the effect of SP, indicating that as well as a neurogenic action, it has a direct action on the vascular smooth muscle. The effect of SP was enhanced by D-Met2-NleS5-enkephalinamide, a delta opiate receptor agonist. The actions of D-Met2-NleS5-enkephalinamide were abolished by pretreatment with hexamethonium, partially abolished by naloxone but were unaffected by atropine. The mu opiate receptor agonist, D-Met2-Pro5-enkephalinamide, inhibited the effects of SP.