Inhibition of CRH-41 release by substance P, but not substance K, from the rat hypothalamus in vitro

Faria, Manuel S.; Navarra, Pierluigi; Tsagarakis, S.; Besser, G. M.; Grossman, Ashley

doi:10.1016/0006-8993(91)90378-9

Cited by 45 publications

(17 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we could not establish whether higher doses of SP could produce more elevated ACTH/cortisol responses, because of the possible inter ference of side effects with the infusion of higher SP amounts [2], Our findings disagree with previous observations in the rat. In this species, the intracerebroventricular ad ministration of SP induces a decrease in plasma ACTH secretion [12], which is thought to depend on the inhi bition of CRH release by SP at a site within the hypo thalamic paraventricular nucleus [13]. The reason for the difference between these and our present results is unknown; it might depend on differences between species or on the different route of administration of SP.…”

Section: Discussioncontrasting

confidence: 56%

“…On the other hand, systemically ad ministered SP can easily reach the anterior pituitary and the median eminence, which are located outside the BBB. In vitro studies in the rat argue against an effect of SP on the release of CRH from the median eminence [13], Furthermore, SP does not stimulate, but rather in hibits ACTH secretion from rat pituitary quarters in vitro [14,15]. In addition, SP has not been detected in measurable concentrations in the rat hypothalamic portal blood [16], However, there might be functional neuroendocrine differences between primates and rats beside the well-known neuroanatomical differences be tween species.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Coiro

Capretti²,

Volpi

et al. 1992

Neuroendocrinology

View full text Add to dashboard Cite

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg^–1/min^–1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg^–1/min^–1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.

show abstract

Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Coiro

Capretti²,

Volpi

et al. 1992

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…After i.c.v. injection, SP inhibits ACTH release [53]probably by reducing CRH release at the hypothalamic level [54]. Treatment with the SP antagonist may thus increase CRH release and subsequently decrease GnRH and LH secretion.…”

Section: Discussionmentioning

confidence: 99%

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

et al. 2000

View full text Add to dashboard Cite

These studies investigated the role of substance P (SP) in the regulation of the hypothalamic-pituitary-ovarian axis in cynomolgus monkeys with normal menstrual cycles. Plasma concentrations of SP were determined in blood samples taken every morning in normally menstruating cynomolgus monkeys throughout the menstrual cycle. There was a significant decreasing linear trend of SP during the follicular phase (cycle day –13 to day 0) and a significant inverse relationship between SP plasma values and plasma 17β-estradiol (E₂) values from day –13 to day 0 of the adjusted cycle. Correspondingly, SP area under the curve was significantly greater during the follicular phase than the luteal phase. In a second experiment, plasma concentrations of E₂, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone and length of cycles were measured after five daily intragastric administrations (10 mg/kg) of an NK₁ receptor (SP receptor) antagonist (RPR 100893; 10 mg/kg) initiated after serum E₂ concentrations had exceeded 125 pg/ml. There was a statistically significant reduction in the amplitude (41% of control) and the area under the curve (37% of control) of the preovulatory LH surge. In addition, there was a reduction of the duration of the LH surge (3 ± 0.1 days in controls vs. 2.1 ± 0.2 days in treated animals). The present results show for the first time that there are significant variations in plasma levels of SP, with a strong negative correlation with serum levels of E₂ during the follicular phase of the cynomolgus monkey, and that endogenous SP has a potentiating role in the interactive hypothalamo-anterior-pituitary mechanisms which lead to the preovulatory LH and FSH surges during the menstrual cycle in the monkey.

show abstract

“…In contrast, CRF mRNA levels decrease in response to repeated stimulation [5]. This effect is dependent on the action of substance P (SP) in parvocellular neurons of the PVN [8] in vivo [6] and in vitro [7]. During chronic stress, SP causes the signal produced by CRF neurons to shift from being CRF-dominated to being more AVP-dominated [2] through centrally located neurokinin-1 (NK1) receptors [8,9].…”

Section: Introductionmentioning

confidence: 97%

Hypothalamic Response to Experimental Allergic Encephalomyelitis: Role of Substance P

Ruocco

Fernandes²,

Namer³

et al. 2003

Neuroimmunomodulation

View full text Add to dashboard Cite

Adjuvant-induced arthritis (AA) is thought to be a model for experimental chronic stress that has as main features decreased adrenocorticotropin hormone (ACTH) plasma levels and a rise in median eminence content of arginine vasopressin (AVP) due to the activity of substance P. In experimental allergic encephalomyelitis (EAE), another chronic stress model, the role of substance P action is not clear. In this paper we tried to clarify the role of substance P in Lewis rats, which are susceptible to this disease. EAE was induced using myelin basic protein plus complete Freund’s adjuvant injected into the hind limbs. One day later injections of an antagonist to substance P (RP 67580), saline, and substance P were administered daily for 12–14 days through a stainless steel cannula into the lateral ventricle of the brain, and then the rats were killed. The rats were divided into groups of controls, sham, diseased controls (no intracerebroventricular injections) and EAE (injected intracerebroventricularly). Plasma was used for the quantification of ACTH and corticosterone but not AVP which was assayed in hypothalamic median eminence extracts. In noninjected diseased rats the plasma levels of ACTH and corticosterone were significantly higher than in noninjected control rats, whereas the AVP concentrations in the median eminence were unchanged. The substance P antagonist did not affect the levels of these hormones in plasma or the median eminence. Substance P decreased the plasma levels of ACTH and corticosterone but did not increase the median eminence content of vasopressin. Administration of the antagonist 30 min before an equivalent dose of substance P increased the plasma levels of the two hormones, but did not change the content of AVP. Based on the lack of response to the antagonist RP 67580 we suggest that the substance P has different roles in EAE and AA at least in the later stages of EAE (after 11 days of immunization).

show abstract

Inhibition of CRH-41 release by substance P, but not substance K, from the rat hypothalamus in vitro

Cited by 45 publications

References 21 publications

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

Hypothalamic Response to Experimental Allergic Encephalomyelitis: Role of Substance P

Contact Info

Product

Resources

About