Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the roles of FK506-binding proteins, receptors for the immunosuppressant FK506, in tachykinin release, we examined the effects of the FK506 derivative ascomycin, [3S-[3R[E(1S,3S,4S)],4S,5R,8S,9E,12R,14R,15S,16R,18S,1 9S,26aR]]-8-ethyl- 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro- 5,19-dihydroxy- 3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16- dimethoxy- 4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotr icosine -1,7,20,21(4H,23H)-tetrone, on the contractility of the rabbit iris sphincter muscle. Ascomycin (10(-7) to 10(-5) M) caused concentration-dependent contractions, which were greatly attenuated by preexposure to rapamycin (10(-5) M), a FK506 receptor antagonist. Similarly, this contractile effect was abolished by preexposure to FK888 (10(-6) M), a tachykinin receptor antagonist, and to capsaicin (10(-5) M), a tachykinin-depleting agent. L-type voltage-dependent Ca2+ channel blockers, nicardipine (10(-5) M) and verapamil (5 x 10(-5) M), inhibited the ascomycin-induced contraction, but the N-type channel blocker omega-conotoxin (10(-6) M) did not. These results suggest that ascomycin stimulates tachykinin release by its binding to FK506-binding proteins and the subsequent activation of L-type Ca2+ channels. Thus, FK506-binding proteins may regulate muscle contractility by altering transmitter release from peripheral tachykininergic nerves.
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PMID:FK506-binding proteins regulate smooth muscle contractility by altering neurotransmitter release. 931 39