The aim of this study was a comparative analysis of five minute episodes of mechanical colonal descending distension (CD) of different degrees, which were provoked by the insertion of a balloon filled with 150 and/or 200 ml of water (CD150 and/or CD200), and plasma cortisol concentration changes as a consequences of the hypothalamo-pituitary-cortico-adrenal axis (HPA) stimulation and nociceptive/stressoric effects. Furthermore, noting the comparative influence of premedication by metabotropic glutamate receptor antagonists via L-isomer and DL-AP3 racemate i.c.v. one min infusion in three different doses (0.2, 0.4 or 0.8 and 4.0, 8.0 or 12.0 mg in toto, respectively) on the plasma cortisol concentration changes, during 120 min of experimentation. The experiment was carried out in four series using 12 female sheep, Polish Merinos, in the anoestrus period (May–June). In the first series (six animals as a control group) the animals had a 200 μl 0.9% NaCl i.c.v. infusion. In the second series they (six animals) had a five min episode of CD by insertion of a balloon filled with 150 and/ or 200 ml of water (CD150 or CD200). In the third series of the experiment six animals had an i.c.v. DL-AP3 or L-AP3 infusion in three different doses (4.0, 8.0 or 12.0 and 0.2, 0.4 or 0.8 mg in toto, respectively), and in the fourth series, ten minutes before CD200, every week. Colon descending distension episodes lasting five minutes provoke a very repetitive, statistically significant increase of plasma cortisol concentration, a critical indicator of the stressoric effect as a consequence of HPA axis stimulation. Undoubtedly DL-AP3 racemate and L-isomer AP3, as metabotropic nonspecific glutamate receptor type-1 antagonists, attenuated this elevation of cortisol, and can be an alternative drug in colonal pain caused by wall distention in sheep.
L-glutamate is one of major excitatory transmitters (along with aspartic, kainate acids and glycine) in the central nervous system and/or the peripheral nervous system. It mediates interaction through the stimulation of various ionotropic receptors families (ligand gated cation channels) and metabotropic receptor families (G-protein coupled). In this review, we describe the molecular composition of these glutamatergic receptors and discuss their neuropharmacology, particularly with respect to their roles in animal social behaviors and, particularly, in aggression. It is also known, that during aggression different interactions occur in the nervous system among glutamate, serotonin, vasopressin, oxytocin, dopamine, GABA and steroid receptors.
The aim of this study was a comparative analysis between a five minute episode of mechanical colonal descending distension, which was provoked by the insertion of a balloon filled with 200 ml of water (CD200), and plasma CA concentration (epinephrine E, norepinephrine – NE and dopamine – DA) changes as a consequence of the sympatho-medullary-adrenal axis stimulation as well as nociceptive/stressoric effects. Furthermore, to note the comparative influence of premedication by metabotropic glutamate receptor antagonists by L-isomer (L-AP3) in the doses of 0.2, 0.4 and/or 0.8mg in toto and/or DL-AP3 racemate i.c.v. one min infusion in three different doses (4.0, 8.0 or 12.0 mg in toto) on the plasma CA concentration changes during 120 min of experimentation. The experiment was carried out in four series using 12 female sheep, Polish Merinos, in the anoestrus period (May–June). In the first series (six animals as a control group) the animals had a 200 μl 0.9% NaCl i.c.v. infusion. In the second series (six animals) they had a five min episode of CD by insertion of a balloon filled with 200 ml of water (CD200). In the third series of the experiment six animals had an i.c.v. DL-AP3 or L-AP3 infusion in three different doses (4.0, 8.0 or 12.0 and 0.2, 0.4 or 0.8 mg in toto, respectively), while in the fourth series, ten minutes before CD200, every week. Colon descending distension episodes lasting five min provoke a very repetitive, statistically significant increase of plasma CA concentration, a critical indicator – after cortisol – of the consequent stressoric effect of the sympatho-medullary adrenal axis stimulation. As a metabotropic nonspecific glutamate receptor type-1 antagonists DL-AP3 racemate and L-isomer AP3 certainly attenuate this elevation of CA, and can be an alternative drug in colonal pain caused by their wall having been distended in sheep. Clinical application of this AP3 must be confirmed by peripheral administration of the drugs.
In the last quarter century, new neurobiological functions of oxytocin (OXY) have been documented. Apart from the important hormonal roles of OXY in the reproductive system (parturition, lactation), it also acts as a neurotransmitter and/or neuromodulator via specific oxytocin receptors(OXYR) in different central nervous structures and peripheral tissues. A high density of OXYR in nervous structures has been confirmed in the amygdala, hypothalamus, hippocampus, nucleus accumbens, striatum, septum, spinal cord, and prefrontal cerebral cortex, which are responsible for states of tension and high emotional intensity, as well as in the adrenal gland – the terminal segment of the hypothalamic-hypophyseal-adrenal axis. OXY is a particularly important neurohormone in the physiopathology of social behaviours and mental states, such as fear, anxiety, aggression, depression, schizophrenia, and autism in humans. The anti-stress and anxiolytic effects of OXY are based mainly on its antagonistic influence on Glu and DA, and on its stimulating influence on the GABAergic central inhibitory system. In addition, OXY inhibits cortisol and CA (stress hormones) release from the cortex and medulla of the adrenal gland during stress.
Stress causes the activation of both the hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal system, thus leading to the release from the adrenal medulla of catecholamines: adrenaline and, to a lesser degree, noradrenaline. It has been established that in addition to catecholamines, the adrenomedullary cells produce a variety of neuropeptides, including corticoliberine (CRH), vasopressin (AVP), oxytocin (OXY) and proopiomelanocortine (POMC) – a precursor of the adrenocorticotropic hormone (ACTH). The aim of this study was to investigate adrenal medulla activity in vitro depending, on a dose of CRH, AVP and OXY on adrenaline and noradrenaline release. Pieces of sheep adrenal medulla tissue (about 50 mg) were put on 24-well plates and were incubated in 1 mL of Eagle medium without hormone (control) or supplemented only once with CRH, AVP and OXY in three doses (10⁻⁷, 10⁻⁸ and 10⁻⁹ M) in a volume of 10 μL. The results showed that CRH stimulates adrenaline and noradrenaline release from the adrenal medulla tissue. The stimulating influence of AVP on adrenaline release was visible after the application of the two lower doses of this neuropeptide; however, AVP reduced noradrenaline release from the adrenal medulla tissue. A strong, inhibitory OXY effect on catecholamine release was observed, regardless of the dose of this hormone. Our results indicate the important role of OXY in the inhibition of adrenal gland activity and thus a better adaptation to stress on the adrenal gland level.