Centrally Administered Tuberoinfundibular Peptide of 39 Residues Inhibits Arginine Vasopressin Release in Conscious Rats

Abstract

Tuberoinfundibular peptide of 39 residues (TIP39) is a recently discovered neuropeptide identified on the basis of its ability to activate the PTH2 receptor, and it is thought to be the brain PTH2 receptor's endogenous ligand. The PTH2 receptor is highly expressed in the hypothalamus, suggesting a role in the modulation of neuroendocrinological functions. PTHrP, which also belongs to the PTH-related peptides family, stimulates arginine vasopressin (AVP) release. In the present study, therefore, we investigated the effect of centrally administered TIP39 on AVP release in conscious rats. Intracerebroventricular administration of TIP39 (10-500 pmol/rat) significantly suppressed the plasma AVP concentration in dehydrated rats, and the maximum effect was obtained 5 min after administration (dehydration with 100 pmol/rat TIP39, 4.32 +/- 1.17 pg/ml; vs. control, 8.21 +/- 0.70 pg/ml). The plasma AVP increase in response to either hyperosmolality [ip injection of hypertonic saline (HS), 600 mosmol/kg] or hypovolemia [ip injection of polyethylene glycol (PEG)] was also significantly attenuated by an intracerebroventricular injection of TIP39 (HS with 100 pmol/rat TIP39, 2.65 +/- 0.52 pg/ml; vs. HS alone, 4.69 +/- 0.80 pg/ml; PEG with 100 pmol/rat TIP39, 4.10 +/- 0.79 pg/ml; vs. PEG alone, 6.19 +/- 0.34 pg/ml). Treatment with naloxone [1.5 mg/rat, sc injection], a nonselective opioid receptor antagonist, significantly reversed the inhibitory effects of TIP39 on AVP release. These results suggest that central TIP39 plays an inhibitory role in the osmoregulation and baroregulation of AVP release and that intrinsic opioid systems are involved in its mechanism.

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

“…Previous studies suggest that TIP39 neurons might be involved in nociceptive processing (Dobolyi et al, 2002;, auditory functions (Dobolyi et al, 2003a;Palkovits et al, 2004), emotional changes (LaBuda et al, 2004, and endocrine regulation (Sugimura et al, 2003;Usdin et al, 2003;Ward et al, 2001). Areas that contain TIP39 neurons are involved in sexual (Coolen et al, 2004;Holstege et al, 2003) and maternal functions (Li et al, 1999;Lin et al, 1998), suggesting that TIP39 may be as well.…”

“…In addition, TIP39 may modulate an affective component of nociception within the brain . TIP39 may also be involved in the hypothalamic regulation of pituitary hormones (Sugimura et al, 2003;Usdin et al, 2003;Ward et al, 2001) and the audiogenic stress response (Palkovits et al, 2004). Centrally administered TIP39 increased the plasma level of adrenocorticotropin and luteinizing hormone (Ward et al, 2001), inhibited the release of arginine vasopressin (Sugimura et al, 2003) and growth hormone , and produced anxiolyticand antidepressant-like effects .…”

“…TIP39 may also be involved in the hypothalamic regulation of pituitary hormones (Sugimura et al, 2003;Usdin et al, 2003;Ward et al, 2001) and the audiogenic stress response (Palkovits et al, 2004). Centrally administered TIP39 increased the plasma level of adrenocorticotropin and luteinizing hormone (Ward et al, 2001), inhibited the release of arginine vasopressin (Sugimura et al, 2003) and growth hormone , and produced anxiolyticand antidepressant-like effects . Areas in which TIP39 neurons are concentrated contain cells that are specifically activated following ejaculation in male rats (Coolen et al, 2004) and in humans (Holstege et al, 2003), or during lactation (Lin et al, 1998).…”

The Distribution and Neurochemistry of the Parathyroid Hormone 2 Receptor in the Rat Hypothalamus

“…TIP39 increased the release of corticotropin-releasing hormone, gonadotropin-releasing hormone and growth hormonereleasing hormone from hypothalamic explants [17]. Intracerebroventricular injection of TIP39 increased the plasma level of adrenocorticotropin and luteinizing hormone [17] and inhibited the release of arginine vasopressin [18] and growth hormone [19]. Further investigation of the physiological functions of TIP39 in the hypothalamus is limited by the lack of information on an anatomical basis for its effects.…”

Development of a rat parathyroid hormone 2 receptor antagonist

“…However there is relatively little experimental data relevant to its physiological role. The few published studies have used administration of pharmacological doses of its putative agonist, tuberoinfundibular peptide of 39 residues (TIP39) [1,9,10,13,14,21], or sequestration of TIP39 with an antibody [1]. A potent and specific antagonist would be a particularly useful reagent for investigation of PTH2 receptor function.…”