[Leu9 psi(CH2NH)Leu10]-neurokinin A (4-10) (MDL 28,564) distinguishes tissue tachykinin peptide NK2 receptors.
The neurokinin A analogue, MDL 28,564 (Asp-Ser-Phe-Val-Gly-Leu-CH2NH-Leu-NH2), inhibited 125I-NKA binding to hamster urinary bladder NK2 receptors with a KI of 130 nM. For rat submaxillary gland NK1 receptors and cerebral cortical NK3 receptors, the KI's for MDL 28,564 were greater than 250 microM and greater than 500 microM, respectively. MDL 28,564 did not relax dog carotid artery (NK1 tissue) or contract rat portal vein (NK3 tissue). In guinea-pig trachea tissues, MDL 28,564 stimulated phosphatidylinositol turnover and induced contraction with maximum effects similar to those of neurokinin A. In hamster urinary bladder tissue, MDL 28,564 stimulated phosphatidylinositol turnover with maximum effect only 10% of that of neurokinin A, did not produce sustained contraction itself and antagonized NKA-induced contraction. MDL 28,564 also produced full contraction in rabbit pulmonary artery (NK2 tissue) but was inactive in rat vas deferens (NK2 tissue). These data with MDL 28,564 are consistent with the NK2 receptors in guinea-pig trachea and rabbit pulmonary artery being different from those in hamster urinary bladder and rat vas deferens.
Buck
S H
SH
Merrell Dow Research Institute, Cincinnati, OH 45215.
Harbeson
S L
SL
Hassmann
C F
CF
Shatzer
S A
SA
Rouissi
N
N
Nantel
F
F
van Giersbergen
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D006224:Cricetinae; D004285:Dogs; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013363:Submandibular Gland / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D010446:Peptide Fragments; D010716:Phosphatidylinositols; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; C066015:MDL 28564; D015288:Neurokinin A