The hamster isolated trachea: a new preparation for studying NK-2 receptors.
Mammalian tachykinins (substance P, neurokinin A and neurokinin B) produced a concentration-related contraction of the hamster isolated trachea with the following order of potency: NKA congruent to NKB much greater than substance P (SP). NKA and NKB were 280 and 203 times more potent than SP, respectively. The action of NKA, NKB or SP was not significantly modified in presence of thiorphan (10 microM), atropine (1 microM), mepyramine (1 microM) or indomethacin (5 microM). [Nle10]NKA-(4-10) or [beta Ala8]NKA-(4-10), two selective NK-2 receptor agonists, displayed good activity while other synthetic agonists, selective for NK-1 or NK-3 receptors, had little or no effect. The contractile response to tachykinins did not undergo appreciable desensitization and was promptly reversed by washing out. These data indicate that NK-2 receptors are the main if not the sole mediators of the response of the hamster isolated trachea to tachykinins, whose action is independent from cholinergic nerves, histamine release or prostaglandin production. Further, no significant peptide degradation by a thiorphan-sensitive mechanism occurs in this organ.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Patacchini
R
R
Rovero
P
P
Meli
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006224:Cricetinae; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013373:Substance P; D001285:Atropine; D015288:Neurokinin A; D015287:Neurokinin B; D015244:Thiorphan; D011738:Pyrilamine; D007213:Indomethacin