A differentiation between peripheral and central neurokinin receptors using phenoxybenzamine.
Concentrations of phenoxybenzamine ranging from 0.33-33 micron produced a competitive block of kassinin-, neurokinin A- and neurokinin B-induced contractions of the guinea-pig ileum with pA2 values of 6.6, 5.6 and 6.2, respectively. Physalaemin- and substance P-induced contractions were insensitive to phenoxybenzamine treatment. Differences in sensitivity to phenoxybenzamine and pA2 values suggest the existence of at least two and possibly three neurokinin receptors in the guinea-pig ileum. Injected intrathecally to mice, phenoxybenzamine blocked neurokinin-induced, but not bombesin- or somatostatin-induced, reciprocal hind limb scratching. Phenozybenzamine was 6-32 times more effective in blocking neurokinin B-induced scratching than substance P, kassinin, physalaemin or neurokinin A-induced scratching. These results suggest that multiple peripheral and central neurokinin receptors can be differentiated from one another by phenoxybenzamine treatment. They also suggest the existence of a distinct neurokinin B receptor in the mouse spinal cord and the apparent identification of a third neurokinin receptor in the guinea-pig ileum.
Vaught
J L
JL
Scott
R W
RW
Jacoby
H I
HI
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D015288:Neurokinin A; D015287:Neurokinin B; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010643:Phenoxybenzamine; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*
D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D010643:Phenoxybenzamine; D013004:Somatostatin; D015288:Neurokinin A; D015287:Neurokinin B; D001839:Bombesin; D009638:Norepinephrine