Tachykinin receptors in the guinea-pig isolated bronchi.
The aim of the study was to assess which tachykinin receptors mediate the contractile response in the guinea-pig isolated bronchi. Experiments with natural tachykinins and receptor-selective tachykinin agonists were performed in the absence or presence of peptidase inhibitors and in bronchi pretreated with phenoxybenzamine. Both NK-1 (substance P, substance P methylester and septide) and NK-2 (neurokinin A, [beta-Ala8]neurokinin A-(4-10) and MDL 28,564) receptor agonists produced concentration-dependent contraction. NK-3 agonists (senktide and [MePhe7]neurokinin B) were active only at high concentrations. Phenoxybenzamine pretreatment reduced the maximal response to NK-1 agonists and produced a rightward shift of the curve to NK-2 agonists, without depression of the maximum. Five tachykinin antagonists selective for the NK-1 (L 668,169) or the NK-2 (MEN 10,207, MEN 10,376, L 659,877 and R 396) receptor were tested against substance P methylester and [beta-Ala8]neurokinin A-(4-10). The results indicated that these receptor-selective antagonists maintain their characteristic even when tested in a multireceptor assay such as the guinea-pig bronchus. The rank order of potency of NK-2 antagonists against [beta-Ala8]neurokinin A-(4-10) was MEN 10,207 = MEN 10,376 greater than L 659,877 much greater than R 396. This pattern, with the observation of the full agonist activity of MDL 28,564, indicates that in addition to NK-1 receptors, NK-2 receptors also are present in the guinea-pig bronchi and belong to the same subtype (NK-2A) as present in the rabbit pulmonary artery.
Maggi
C A
CA
Pharmacology Department, Research Laboratories, A. Menarini Pharmaceuticals, Florence, Italy.
Patacchini
R
R
Quartara
L
L
Rovero
P
P
Santicioli
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D017981:Receptors, Neurotransmitter / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D009842:Oligopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D010643:Phenoxybenzamine; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; C033611:substance P, methyl ester-; C054725:septide; D015288:Neurokinin A; D011761:Pyrrolidonecarboxylic Acid