Effects of histamine on phosphoinositide metabolism in chick cerebral cortex.

Effects of histamine (HA) and agonists of HA receptors on phosphoinositide metabolism in chick cerebral cortex have been studied using two approaches - measurement of inositol 1,4,5-trisphosphate (IP3) level by a specific and sensitive IP3 receptor radioassay, and analysis of [3H]inositol phosphates accumulation in cortical slices prelabeled with myo-[3H]inositol. HA concentration-dependently elevated IP3 levels in slices of chick cerebral cortex. The effect of HA was mimicked by 2-methylHA, a selective agonist of H1-HA receptors, and blocked by mepyramine, an H1 receptor antagonist. 4-MethylHA and Ralpha-methylHA, selective agonists of H2- and H3-HA receptors, respectively, did not affect IP3 level in the chick cerebrum. In cerebral cortical slices prelabeled with myo-[3H]inositol, 2-methylHA significantly stimulated [3H]inositol phosphates accumulation, whereas HA only slightly and non-significantly increased phosphoinositide metabolism. It is suggested that phospholipase C-coupled H1-HA receptors are present in the chick cerebral cortex, yet their number seems to be a small one.

Characterization of beta-adrenergic receptors in duck cerebral cortex.

beta-adrenoceptor binding sites were characterized in duck cerebral cortex by an in vitro binding technique, using [3H]dihydroalprenolol ([3H]DHA) as a receptor-specific radioligand. The specific binding of [3H]DHA to duck cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot suggesting binding to a single class of receptor binding sites with high affinity (Kd = 1.18 nM) and high capacity (Bmax = 162 fmol/mg protein). Competition studies showed the following relative rank order of potency of various compounds to inhibit the [3H]DHA binding: antagonists--ICI 118,551 > S(-)-propranolol >> betaxolol, yohimbine, WB-4101, prazosin, mianserine; agonists--isoprenaline approximately equal to fenoterol > salbutamol >> clonidine, phenylephrine. The obtained data suggest that in duck cerebral cortex beta-adrenergic receptors (like those described in brains of chick and pigeon) are of the beta 2 subtype. This is in contrast to what has been reported for the mammalian brain, where--among beta-adrenoceptors--the beta 1 subtype is predominant.

A synergistic interaction between histamine and vasoactive intestinal peptide (VIP) on cyclic AMP production in the chick pineal gland.

The effects of vasoactive intestinal peptide (VIP) and histamine, alone and in combination, on cyclic AMP formation have been studied in selected tissues of the central nervous system (CNS) of chick. VIP strongly stimulated cyclic AMP production in the pineal gland, moderately in the retina (maintained in "eye-cup" preparations), and had no effect in cerebral cortical slices. Combination of VIP with forskolin produced a synergistic response in the pineal gland; in the cerebral cortex VIP did not influence the elevation of cyclic AMP production evoked by forskolin, histamine and isoprenaline. Histamine stimulated cyclic AMP synthesis in the all tested CNS tissues, showing the following order of sensitivity to the amine: pineal gland > cerebral cortex > retina. The effects of histamine were stronger in the presence of forskolin. A combination of VIP and histamine produced the cyclic AMP response in the pineal gland clearly more than additive; such a synergistic interaction was antagonized by aminopotentidine, an accepted in mammals H2-histamine receptor blocker. It is concluded that both VIP and histamine can be considered as functionally important neuromodulators in avians (similar to mammalian species). These two substances may play in concert to regulate the pineal physiology in avian species.

Histaminergic and noradrenergic control of cyclic AMP formation in the pineal gland and cerebral cortex of three avian species: cock, duck, and goose.

The goal of the present study was to examine the effects of forskolin (FOR), histamine (HA), L-noradrenaline (NA), isoprenaline (ISO) and dopamine (DA) on cyclic AMP formation in whole pineal glands and cerebral cortical slices of cock, duck and goose. HA (100 muM) and FOR (10 muM) potently increased cyclic AMP production in the pineal glands of all studied avian species, showing a synergistic interaction when applied together. HA at the dose of 1 mM significantly stimulated adenylyl cyclase activity in the membrane preparations of cock pineal glands while lower concentrations were ineffective. HA markedly enhanced cyclic AMP formation in cerebral cortex of cock (an effect being potentiated for FOR), but did not affect the nucleotide production in this brain structure of duck and goose. DA (100 muM) had no effect, NA (100 muM) only moderately (5-22% increased, where ISO (10muM) significantly (by 50-90%) enhanced cyclic AM_ synthesis in avian cerebral cortex. Propranolol (1 muM) antagonized all these effects, while preincubation with yohimbine and prazosin significantly enhanced NA action in cortical slices of duck and goose.

Effects of calcium ions and substances affecting Ca2+ -related mechanisms on histamine-evoked stimulation of cyclic AMP formation in chick pineal gland.

In avian central nervous system (CNS), and particularly in the pineal gland, histamine (HA) potently stimulates synthesis of cyclic AMP in intact tissue, and only weakly affects adenylyl cyclase activity in membrane preparation. In this work, we focussed on calcium (Ca2+) as a possible link in the mechanism through which HA affects cyclic AMP generation in the chick pineal. The problem was studied in two sets of experiments where the action of HA on the pineal cyclic AMP was tested: (1) in the incubation medium containing various compounds influencing Ca2+ influx and/or Ca2+ intracellular concentration/action (Ca2+ -ionophore calcimycin, Ca2+ -channel agonist Bay-K 8644, Ca2+ -channels blockers: diltiazem, verapamil, nifedipine and omega-conotoxin-GVIA, CaCl2, EGTA in the absence of CaCl2 in the incubation medium, as well as calmodulin inhibitors: calmidazolium and W-7), and (2) in a CaCl2-free incubation medium yet containing different concentrations of BaCl2, CdCl2, CoCl2, MgCl2, and NiSO4. The results of the first series were mostly negative; an exception was the inhibiton of the HA-evoked cyclic AMP formation observed in the presence of 5.2 and 10.4 mM CaCl2 In the second series of experiments, divalent cations (however with the exception of Mg2+, which was inactive at concentrations up to 15.6 mM) inhibited the HA-evoked cyclic AMP production, with the following rank order of potency: Cd2+ >> Co2+ >> Ni2+ > Ba2+. The inhibitory effect of CdCl2 was prevented by nifedipine. Taken together, the present data suggest that intracellular Ca2+ -related mechanisms are not of major importance in the HA action on cyclic AMP synthesis in the chick pineal. It could be suspected that the inhibition of the HA-driven cyclic AMP formation by high concentrations of Ca2+, and other divalent cations, probably resulted from their direct inhibitory interaction with the catalytic site of the pineal adenylyl cyclase.

Histamine-stimulated cyclic AMP formation in the chick pineal gland: role of protein kinase C.

The role of protein kinase C (PKC) in histamine (HA)-stimulated cyclic AMP formation in intact chick pineal glands was investigated. In the pineal gland of chick HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA potently increased cyclic AMP accumulation in a concentration-dependent manner. Treatment of intact glands with PKC inhibitors, i.e. chelerythrine and stautosporine, reduced the stimulatory effect of the HA-ergic compounds on cyclic AMP formation. HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA significantly increased inositol-1,4,5-trisphosphate (IP3) levels in intact chick pineal glands, indicating their activities on phospholipase C and 1,2-diacylglycerol formation. The stimulatory effect of HA on IP3 levels was antagonized by aminopotentidine, a potent blocker of H2-like HA receptors in avian pineal gland. Preincubation of chick pineal glands with a PKC activator, 4 beta-phorbol 12, 13-dibutyrate (4 beta-PDB), enhanced the accumulation of cyclic AMP elicited by HA, 2-methylHA, 4-methylHA, and N alpha, N alpha-dimethylHA. On the other hand, 4 beta-phorbol, inactive on the PKC, was ineffective. Our results point to the possibility that PKC is involved in the regulation by HA of cyclic AMP synthesis in the pineal gland of chick. Furthermore, the cyclic AMP response to pineal HA receptor stimulation can be positively modulated by a concomitant activation of the PKC pathway.

Histamine in the chick pineal gland: origin, metabolism, and effects on the pineal function.

The chick pineal gland contains histamine and tele-methylhistamine. The levels of both substances are elevated after treatment of chicks with the amino acid precursor of histamine, L-histidine (1 g/kg, ip). In control and L-histidine-loaded animals the pineal levels of histamine and tele-methylhistamine are higher in light-exposed than in dark-adapted animals (measured at the end of the light phase and in the middle of the dark phase of 12 hr light, 12 hr dark illumination cycle, respectively). The chick pineal gland contains histamine-immunofluorescent cells displaying mast cell morphology; they are seen in the vicinity of the capsule and in the parenchyma. Enzymatic studies showed the presence of the activity of histamine synthesizing and inactivating enzyme, i.e., L-histidine decarboxylase (HDC) and histamine-methyltransferase (HMT). The detected enzyme activities were sensitive to specific inhibitors of HDC (alpha-fluoromethylhistidine and alpha-hydrazinohistidine) and HMT (quinacrine and metoprine); inhibitors of aromatic amino acid decarboxylase alpha-methyl-DOPA and NSD-1015 were inactive on HDC. Exogenous histamine added to organ-cultured chick pineals strongly stimulated endogenous cyclic AMP accumulation and moderately increased melatonin secretion. The data, considered collectively, suggest that in avians histamine, probably originating from the pineal mast cell compartment, may function as a regulator of pineal gland activity.

The presence of histamine and tele-methylhistamine in the pineal gland of chick.

The levels of histamine (HA) and tele-methylhistamine (t-MeHA) in chick pineal gland were measured by RIA at two time points, i.e. at the end of the light (L) phase and in the middle of the dark (D) phase of 12 h: 12 h L:D cycle. The chick pineal gland showed high HA levels (12.19 and 13.09 ng/pineal at L and D, respectively). The t-MeHA content of chick pineal gland was about 20-times lower than HA level (650.2 and 536.4 pg/pineal at L and D, respectively). An aminoacid precursor of HA, L-histidine (1 g/kg, ip), given to chicks during L or D significantly increased both HA and t-MeHA content of the pineal gland. The L-histidine-evoked elevations in HA level were 2-4-times higher than changes in t-MeHA content. Enzymatic study showed the presence in chick pineal of a moderate activity of L-histidine decarboxylase (HDC), and well expressed activity of HA-methyltransferase (HMT), HA synthesizing and inactivating enzyme, respectively, which suggests that both HA and t-MeHA may be produced within the gland. It is suggested that the metabolic dynamics of the pineal HA may be higher during lighthours than darkhours of the daily light:dark illumination cycle.

Arylamine and arylalkylamine N-acetyltransferases in retina, pineal gland, brain and liver of chicks: a comparative study.

Regulation of arylamine N-acetyltransferase (A-NAT) and arylalkylamine N-acetyltransferase (AA-NAT) was examined in retina, pineal gland, brain and liver of chicks. Enzyme activities were determined using as substrates p-phenetidine and procainamide for A-NAT, tryptamine and phenethylamine for AA-NAT. The activity of A-NAT in all tissues studied does not appear to be regulated by a light-dark cycle. On the other hand, AA-NAT showed distinct light-dark dependent changes (with high values at night) in the retina and pineal gland, but not in brain and liver. The nocturnal increase of retinal and pineal AA-NAT activity was prevented by cycloheximide; the drug did not affect A-NAT activity in these tissues. Treatment of light-adapted chicks with aminophylline significantly increased AA-NAT activity of the retina and pineal gland, without altering the enzyme activity in brain and liver. In these animals, the activity of A-NAT (procainamide) did not change in any tissue studied, whereas the enzyme activity measured using p-phenetidine as a substrate did decrease but only in the retina. A similar pattern of changes in retinal A-NAT and AA-NAT activities was observed after intraocular injection of d,b-cAMP. The rate of inactivation at 4 degrees C was significantly slower for AA-NAT than A-NAT. NATs from brain and liver displayed the highest and lowest, respectively, liability in the cold. The results indicate that the chick retina contains both A-NAT and AA-NAT. The two enzymes have distinct characteristics and the regulation of their activities is different. The retinal A-NAT is similar to A-NAT present in other tested tissues; however, AA-NAT can be induced at night only in the retina and pineal gland. It is suggested that there are two forms of retinal A-NAT, and that, under specified conditions, the activity of one form (A-NAT; p-phenetidine) may be regulated in an opposite manner to AA-NAT activity.

Light-induced suppression of nocturnal serotonin N-acetyltransferase activity in chick pineal gland and retina: a wavelength comparison.

Effects of white and monochromatic (blue-434 nm, green-548 nm, and red-614 nm) lights on the nighttime retinal and pineal NAT activity were examined in chicks. The potency of the tested lights to suppress NAT activity was similar for the retina and pineal gland, with a following rank order: white > green > blue > or = red. The studied tissues of chick were far less sensitive to pulses of monochromatic light than the rat pineal gland. The potency of light to decrease pineal NAT activity of rat was: white > green >> blue > red. In chicks, the suppression of the nocturnal NAT activity produced by a short 5-min pulse of monochromatic light was completely reversible in the pineal gland, and partially reversible in the retina. Our data suggest the existence of some differences between birds and mammals in terms of sensitivity and mechanisms involved in the light-induced suppression of melatonin biosynthesis.