Disease relevance of Senktide

• Conversely, intrathecal senktide (10 nmol) induced thermal hyperalgesia, indicated by decreased withdrawal latency to radiant heat [1].
• R116301 did not affect senktide-induced miosis (>5 mg/kg, s.c.) in rabbits, confirming the absence of an interaction with the NK(3) receptor [2].
• 2. Tachycardia was elicited by the NK(1) ([Sar(9),Met(O(2))(11)]SP) and NK(2) ([betaAla(8)]NKA(4-10)) agonists at 25 and 100 pmol while the NK(3) agonist (senktide, 50 and 100 pmol) had no significant effect [3].
• The ID injection of the selective NK1, SP methyl-ester (1-30 nmol), NK2, [beta-Ala8]-neurokinin A4-10) (beta-Ala, 0.3-30 nmol), or NK3, senktide (1-10 nmol) agonists, caused extensive edema formation with mean ED50s of 0.48 nmol, 0.41 nmol, and 0.18 nmol, respectively [4].
• The microinjection of 1-10 ng of suc-[Asp5, Me-Phe8]-SP(6-11) (senktide, a selective neurokinin B receptor peptide) into the NTS caused long-lasting hypertension and tachycardia [5].

Psychiatry related information on Senktide

• 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 tachykinin receptors in wet-dog shake behaviour [6].
• The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice [7].

High impact information on Senktide

• RESULTS: In awake rats, intraperitoneal administration of the NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agonist senktide increased, both the rectocolonic inhibitory reflex and abdominal contractions produced by colorectal distention [8].
• The NK-3 receptor homolog bound [3H] senktide with a Kd of 39 nM, similar to that of the NK-3 receptor [9].
• Tachykinin peptides stimulated both inositol phospholipid hydrolysis and arachidonic acid release at NK-3 and NK-3 receptor homolog cell lines, with similar rank orders of potency of [MePhe7] neurokinin B = neurokinin B = senktide > NKA = substance P [9].
• NKB and [Lys5,methyl-Leu9,Nle10]NKA(4-10) displaced [3H]ALIE-124 binding but with lower potency, whereas senktide had no affinity [10].
• The selective NK-1 receptor agonist [Sar-9, MetO2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [betaAla-8]-NKA(4-10) or the selective NK-3 agonist senktide [11].

Chemical compound and disease context of Senktide

• Senktide blocked the effects of cocaine on locomotor activity, but enhanced the cocaine effects on exploratory activity, aerial scanning frequency, and terrestrial glance behavior [12].

Biological context of Senktide

• Binding studies were performed in the presence of SR 48968 (NK(2) antagonist) and senktide (NK(3) agonist) because [(125)I]NKA also labels peripheral NK(2) binding sites and, as shown in this study, central NK(3) binding sites [13].
• 5. Using voltage clamp analysis, capsaicin and senktide analogue evoked an inward current and an increase in membrane conductance at the resting membrane potential [14].
• Thus, the increased skin temperature associated with intrathecal senktide was insufficient to account for the thermal hyperalgesia observed [1].
• Intrathecal senktide produced vasodilation and increased skin temperature in the hind paw [1].
• The intrathecal administration of senktide (10 nmol) did not alter the monosynaptic reflex elicited by stimulating the L5 dorsal root at an intensity that was at the threshold for activating A fibers [15].

Anatomical context of Senktide

• Although intrathecally administered senktide, an agonist at the neurokinin3 receptor, attenuates withdrawal responses to noxious stimuli in the restrained animal, senktide increases motor neuron activity in spinal cords of neonatal rats and facilitates the electrically-evoked nociceptive flexor reflex in the adult rat [1].
• This modified dipeptide has a Ke of 7 nM in blocking senktide-induced increases in intracellular calcium levels in human NK3 receptors stably expressed in CHO cells [16].
• Senktide-induced contractions of isolated guinea pig ileum were also blocked by low concentrations of ZD6021 [17].
• Additional regions that contained elevated FLI following icv injection of senktide, relative to saline injection, included the cerebral cortex, lateral hypothalamic nucleus, suprachiasmatic nucleus, ventral tegmental area, substantia nigra, inferior colliculus, locus coeruleus, zona incerta, and arcuate nucleus [18].
• In the human bronchus and hamster trachea, [beta-Ala8]-NKA4-10 was the most potent agonist, whereas ASMSP and senktide analog failed to elicit contractions greater than 50% of the maximum response even at concentrations reaching 1 to 3 x 10(-4) M [19].

Associations of Senktide with other chemical compounds

• The rank order of tachykinin peptides competing for [3H]senktide binding at the NK-3 receptor homolog was [MePhe7]neurokinin B > senktide > substance P = neurokinin A > neurokinin B [9].
• These compounds, namely septide [( pGlu6, Pro9]substance P6-11 hexapeptide), which preferentially acts on the NK-1 (SP-P) receptor, and senktide (succinyl-[Asp6,Me-Phe8] substance P (6-11) hexapeptide), which selectively acts on the NK-3 (or SP-N) receptor, were now used to identify the tachykinin receptors present in several smooth muscle systems [20].
• 5. MEN 10,627 inhibited the response to [beta-Ala8]NKA 4-10 but not to SP, SPME, NKA, NKB or senktide [21].
• Septide as well as senktide were found to be devoid of activity in the electrically stimulated rat vas deferens, showing that, in this preparation, which is the prototype NK-2 (or SP-E) system, tachykinin-induced contraction is not mediated via NK-1 or NK-3 receptors [20].
• The NK-3 tachykinin receptor agonist senktide elicits 5-HT-mediated behaviour following central or peripheral administration in mice and rats [22].

Gene context of Senktide

• GR64349 and senktide (agonists at NK2 and NK3 receptors respectively) also inhibited K+ currents, but only at concentrations which were several orders of magnitude greater than GR73632, suggesting that current inhibition was mediated via NK1 receptors [23].
• Both NK-1 (GR73632) and NK-3 (senktide) agonists induced a variety of behavioural effects which appeared to compete with the drinking response [24].
• Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries [7].
• 4. The NK3 tachykinin receptor agonist, senktide, contrasts with the NK1 receptor agonists in that it elicited only wet-dog shakes, at doses ranging from 0.32 to 1.25 micrograms [25].
• In contrast, the NK3-selective hexapeptide, senktide, was recognized only when transmembrane segment III and IV from the NK3 receptor were incorporated into the chimeric constructs [26].

Analytical, diagnostic and therapeutic context of Senktide

• Intraventricular injections of 200 ng senktide had no significant effect on baseline MAP, but significantly decreased the gain of the baroreflex in all three rat strains whereas the 100 ng dose had no effect on the baroreflex [27].
• Similar decreases in intragastric pressure were noted after the microinjection of [Sar(9),Met(O(2))(11)]SP (NK(1)R agonist; 135 pmol) but not senktide (NK(3)R agonist; 135 pmol) or vehicle [28].
• Slow EPSPs evoked by electrical stimulation of circumferentially oriented presynaptic nerves were mimicked by application of senktide, an NK(3)R agonist [29].
• Septide and senktide, administered by lumbar puncture and by indwelling catheter, produced identical results [30].
• Other rats were implanted with microdialysis probes adjacent to the paraventricular nucleus (PVN), and dialysate and plasma OT concentrations were determined before and during administration of senktide through the dialysis probe [31].

References