ISSN:
1573-6903
Keywords:
TRH
;
substance P
;
tachykinins
;
rat brain
;
amygdala
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Binding sites for thyrotropin-releasing hormone (TRH) were labelled with [3H](2-Me-His3)TRH ([3H]MeTRH) on membranes from rat brain regions at 0°C for 5 h. Amygdaloid membranes bound [3H]MeTRH with high-affinity (K d=3.1±0.5 nM (n=4)). Five TRH analogs competed for this binding with the same rank order and with affinities that matched the pharmacological specificity of pituitary TRH receptors. Substance P (SP) and its C-terminal fragments reduced amygdaloid TRH receptor binding in a concentration dependent manner (IC50 for SP=65 μM). The rank order of potency of SP analogs at inhibiting TRH receptor binding was: SP〉nonapeptide (3–11)〉hexapeptide (6–11)〉heptapeptide (5–11)〉pentapeptide (7–11). However, other tachykinins were inactive in this system. SP was a potent inhibitor of [3H]MeTRH binding in hippocampus〉 spinal cord〉retina〉n. accumbens〉hypothalamus〉amygdaloid〉olfactory bulb ≥pituitary〉pons/medulla in parallel assays. In amygdaloid membranes SP (50 μM) reduced the apparent maximum receptor density by 39% (p〈0.01) without altering the binding affinity, and 100 μM SP induced a biphasic dissociation of [3H]MeTRH with kinetics faster than those induced by both TRH (10 μM) and serotonin (100 μM). In contrast, other neuropeptides such as neurotensin, proctolin, angiotensin II, bombesin and luteinizing hormone releasing hormone did not significantly inhibit [3H]MeTRH binding to amydaloid membranes. Thus, the SP site with low affinity in the rat brain is not like any of the previously described tachykinin/neurokinin binding sites but resembles the site found on neuroblastoma cells (108CC15) and on adrenal chromaffin cells that modulate cation permeability and nicotinic receptors respectively. The physiological role of these atypical SP sites in the rat brain remains to be determined.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00965752
