Biomedical subjects

T Karashima

Publications and source records attributed to T Karashima.

At least 55 records · Page 3Linked to original sources

PubMed1989

The existence of a platelet-activating factor (Paf-acether)-like substance in blister fluid derived from patients with bullous pemphigoid as demonstrated by human platelet aggregation techniques.

We investigated the presence of a platelet-activating factor-like substance in blister fluid obtained from patients with bullous pemphigoid. Human platelet aggregation activity was present in blister fluids obtained from 4 out of 6 patients with bullous pemphigoid and in blister fluids obtained from 3 cases with contact dermatitis. Platelet aggregation activity of pemphigoid blister fluids was inhibited by pretreatment with lyso-PAF, which is a precursor metabolite of platelet activating factor. The activity of blister fluids obtained from patients suffering from contact dermatitis was not inhibited by precursor. Blister fluid obtained from burn lesions and blisters of normal skin induced in the suction revealed no platelet aggregation activity. These results suggest that platelet-activating factor or a similar substance is present in the blister fluid obtained from suffered bullous pemphigoid.

Adult↗

PubMed1988

Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically.

Anaphylaxis↗

PubMed1988

Protective effects of analogs of luteinizing hormone-releasing hormone against chemotherapy-induced testicular damage in rats.

Possible protective effects of analogs of luteinizing hormone-releasing hormone (LH-RH) against testicular damage caused by various cytotoxic agents were investigated in rats. The agonist [D-Trp6]LH-RH (in which Gly-6 is replaced by D-tryptophan) and the antagonist N-Ac-[D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH were administered for 12 weeks: [D-Trp6]LH-RH was given once a month in the form of long-acting microcapsules liberating 25 micrograms of agonist per day, and the antagonist was injected s.c. at a dose of 1000 micrograms per kg of body weight per day for the first 3 weeks and, thereafter, at a dose of 500 micrograms per kg of body weight per day. After a recovery period of 3 months, most seminiferous tubules in the antagonist-treated group showed a normal morphology, while patches of tubules in the agonist-treated group continued to show some suppression of spermatogenesis. Administration of busulfan, cisplatin, or cyclophosphamide produced only a reversible testicular injury, and pretreatment with LH-RH analogs seemed to temporarily enhance the tubular damage. Administration of procarbazine (200 mg per kg of body weight per week for 6 weeks) resulted in decreased testicular weights and increased serum LH levels 1 and 3 months after the discontinuation of treatment. The histology showed severe diffuse damage to seminiferous tubules. The germinal cells completely disappeared and the Sertoli cells were markedly degenerated. This damage was not restored even after a recovery period of 5 months. Some animals were pretreated for 6 weeks with the agonist or antagonist and then received procarbazine for 6 weeks while administration of analogs was continued. In these animals, the decrease in testicular weights and increase in serum LH levels after procarbazine were less marked than in the group not pretreated with the analogs. Three and 5 months after cessation of treatment, a large number of tubules showed a complete restoration of structural morphology in 30-45% of the animals that received procarbazine and the LH-RH agonist or antagonist. These results indicate that pretreatment with LH-RH analogs may protect testes against damage caused by some cytotoxic agents.

Animals↗

PubMed1987

Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release.

Biological activities of highly potent octapeptide analogs of somatostatin (SS), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), were investigated in male rats. When analog RC-160 was administered to rats in which serum growth hormone (GH) levels were elevated by pentobarbital anesthesia, a dose-related inhibition of GH was obtained at dose range of 0.1 to 2.5 micrograms/kg. The time course of GH inhibition by RC-160, RC-121 and SS-14 was studied in rats treated with phenobarbital, morphine and chlorpromazine. Analogs RC-160 and RC-121 induced a prolonged inhibition of GH levels, in contrast to SS-14, whose effect was short-lived. The analogs suppressed the GH level for more than 2 hr, the peak inhibition being seen 30 to 60 min after the injection. The effects of analogs RC-160 and RC-121 on insulin secretion were observed in rats, in which insulin levels had been elevated by intravenous administration of glucose (500 mg/rat). Administration of RC-160 suppressed insulin secretion, dose-dependently, maximum but not complete inhibition being achieved at a dose of 100 micrograms/kg. In this model, RC-160 and RC-121, in doses of 30 micrograms/kg, induced a similar inhibition of insulin release as 200 micrograms/kg of SS-14, whose action of SS-14 was transient. The effect of analog RC-160 on glucagon release was studied in rats with glucagon levels elevated by hypoglycemia. RC-160 suppressed the secretion of glucagon, the inhibition being dose-dependent in the range of 0.1 to 2 micrograms/kg. Doses of 2 and 10 micrograms/kg of this analog completely suppressed the hypoglycemia-induced glucagon release. These results indicate that analogs RC-160 and RC-121 possess prolonged and enhanced biological activities, the former analog showing a high selectivity in inhibiting GH and glucagon release in vivo as compared with that of insulin secretion.

Animals↗

PubMed1987

Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats.

The effect of the repeated or continuous administration of an analog of GH releasing factor (GH-RF), D-Tyr-1, D-Ala-2, Nle-27, GH-RF(1-29)-NH2 (DBO-29), on the subsequent response to this peptide was investigated in pentobarbital-anesthetized male rats. A sc administration of this analog induced a greater and more prolonged GH release than doses 10 times larger of GH-RF(1-29). The GH increase after sc injection of 10 micrograms/kg bw of the analog was greater than that induced by iv administration of 2 micrograms/kg bw of GH-RF(1-44). Pretreatment with 10 micrograms/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 micrograms/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 micrograms/kg bw, sc twice a day, 5 days per week for 4 weeks, significantly diminished the GH release in response to a sc injection of the analog (10 micrograms/kg bw), as compared to vehicle-pretreated controls (P less than 0.01). On the other hand, a continuous sc administration of 0.4 micrograms/h of the analog to intact rats for 7 days did not result in a decrease in GH response to a sc injection of the analog (10 micrograms/kg bw). Since the rats injected repeatedly with the analog for 4 weeks still showed a marked, although somewhat reduced response, analogs of this type may be useful clinically.

Animals↗

PubMed1987

Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.

Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 micrograms/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 micrograms of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. In spite of pretreatment with [D-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

Animals↗

PubMed1987

Superactive octapeptide somatostatin analogs containing tryptophan at position 1.

We synthesized a series of octapeptide analogs of somatostatin, containing N-terminal tryptophan or another amino acid followed by the hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys and a C-terminal threoninamide or tryptophanamide. After purification by HPLC, the inhibitory activities of these analogs on the release of growth hormone (somatotropin) in rats were determined in vivo. The eight octapeptides with an N-terminal tryptophan residue were found to have a greater inhibitory effect than somatostatin. The most potent of these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, was 94.3 times more active than somatostatin. The other analogs, in order of decreasing potency, were Ac-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, Ac-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, Ac-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2, and D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2. The growth hormone inhibitory activity of these analogs was from 53.7 to 11.6 times greater than that of somatostatin. The octapeptides containing D- or L-tryptophan at the N-terminus, phenylalanine at position 3, and threonine at position 6 exhibited a greater inhibitory effect on growth hormone release than that of the analogs with tyrosine and valine at positions 3 and 6, respectively. Substitution of D-tryptophan for D-phenylalanine at the N-terminus in the octapeptide containing phenylalanine in the third, threonine in the sixth, and threoninamide in the C-terminal position also increased the growth hormone-release inhibitory activity. Time-course assay showed that D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I), in a dose of 1 microgram/kg of body weight, inhibited the release of growth hormone for at least 3 hr. In view of their high activity and prolonged duration of action, some of these analogs could be useful clinically.

Animals↗

PubMed1987

Inhibitory effects of somatostatin analogs on prolactin secretion in rats pretreated with estrogen or haloperidol.

The effect on prolactin (PRL) secretion of acute administration of new octapeptide analogs of somatostatin (SS) with an enhanced and prolonged growth hormone inhibitory activity was investigated in rats under various pretreatment conditions with estrogen and antidopaminergic drugs. Analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), at a dose of 5 micrograms/100 g body wt, did not decrease basal PRL levels in thiopental-anesthetized female rats, untreated or treated with estrogen benzoate (EB) (8 micrograms/rat) for 5 days. When haloperidol was used to elevate PRL level, a single injection of RC-121 inhibited PRL release in EB-pretreated female rats or untreated female and male rats. Analog D-Phe-Cys-Trp-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), which has a potency similar to RC-121 in the tests on inhibition of GH, in a dose of 0.2 microgram/100 g body wt, did not lower the elevated PRL level induced by alpha-methyl-p-tyrosine and/or pretreatment with EB (100 micrograms/rat, 3 and 6 days before) in pentobarbital-anesthetized male rats. However, both analogs RC-121 and RC-160, in doses of 0.2 microgram/100 g body wt, decreased the PRL levels elevated by prolonged pretreatment with EB (100 micrograms/rat, twice a week for 3 weeks) in male rats. These results indicate that acute administration of these SS analogs can induce a prolonged inhibition of PRL release when PRL is acutely elevated by haloperidol or chronically elevated by 3 weeks of estrogen administration. Future additional studies are required to investigate the effects of chronic administration of these SS analogs on PRL levels.

Animals↗

PubMed1986

Postoperative plasma GH levels and restoration of GH dynamics in acromegalic patients surgically treated by the transsphenoidal approach.

In 44 patients with acromegaly treated by transsphenoidal pituitary microsurgery, the relationship between changes in pre- and post-operative GH dynamics and postoperative fasting plasma GH levels was examined to clarify which is the optimal approach for evaluating postoperative removal of the tumour. TRH, LHRH and bromocriptine tests, which act directly on the pituitary somatotroph, and the oral glucose tolerance test (oGTT) and insulin tolerance test (ITT), which act via hypothalamus, were carried out pre- and post-operatively. Abnormal responses postoperatively were found in most patients with fasting postoperative plasma GH over 5 ng/ml. In 24 patients with postoperative fasting plasma GH level of 5 ng/ml or below, 7 of 17 (41%) showed abnormal responses in the TRH test, 2 of 5 (40%) in the LHRH test and 3 of 13 (23%) patients in the bromocriptine test. All patients with a fasting plasma GH level less than 10 ng/ml, except for those with panhypopituitarism, showed normal responses to ITT and the paradoxical increases with the oGTT were absent. These results indicate that abnormal responses caused by a direct action on adenoma cells do not necessarily disappear even when the fasting plasma GH level is below 5 ng/ml. Abnormal responses caused by indirect actions, through the hypothalamus, disappear when the level is less than 10 ng/ml.

Acromegaly↗

PubMed1986

Long-term bromocriptine therapy and predictive tests in acromegaly.

The value of predictive tests in bromocriptine therapy and the effects of long-term bromocriptine therapy were investigated in acromegalic patients. In 72 acromegalic patients, there was a tendency for patients with a plasma GH response to TRH or with an elevated basal plasma PRL level, but without a plasma GH response to LHRH, to have a plasma GH response to bromocriptine, though statistical analysis did not reveal a significant difference. Acute and chronic effects of bromocriptine were significantly interrelated, while the chronic effect of bromocriptine and abnormal plasma GH response to TRH or elevated plasma PRL levels were not, in 18 acromegalic patients. These results suggest that the acute bromocriptine test is a better predictor than the TRH test and plasma PRL levels for evaluating the effects of chronic bromocriptine therapy. To maintain the low plasma GH levels, increasing doses of bromocriptine were needed in most patients, and failure to control the elevated GH level despite increasing doses was observed in 2 of 18 patients.

Acromegaly↗

PubMed1985

Specific somatostatin receptors on human pituitary adenoma cell membranes.

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.

Adenoma↗

PubMed1985

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia.

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.

Acromegaly↗

PubMed1984

Comparison of growth hormone responses to human pancreatic growth hormone releasing factor and other pharmacological stimuli in acromegalic patients.

Synthetic human pancreatic growth hormone releasing factor (pGRF) was administrated intravenously to 14 acromegalic patients, and the response of plasma GH to pGRF was compared with that to TRH, GnRH or other GH-stimulating agents in these patients. Three patients hyperresponded (more than 8 times), 4 patients responded (2-4 times), 4 patients hyporesponded (1.5-2.0 times) and 3 patients did not respond at all. There was no correlation between the responses to TRH and pGRF, however, an intimate relationship was observed between responses to pGRF and GnRH in the patients who hyperresponded to pGRF. A patient not responding to pGRF showed a marked response to insulin or clonidine and another patient not responding to insulin or clonidine did respond to pGRF. Similarly, some patients not responding to FK 33-824, a met-enkephalin analog, or arginine did respond to pGRF.

Acromegaly↗

PubMed1984

Suppressive effects of cholecystokinin and bombesin on growth hormone and prolactin secretion in urethane-anesthetized rats.

The effects of cholecystokinin octapeptide (CCK) and bombesin on rat plasma growth hormone (GH) and prolactin (PRL) levels were investigated with the animals under urethane anesthesia. Intraventricular administration of both CCK (0.3 micrograms) and bombesin (2 micrograms) completely suppressed the GH secretion induced by FK 33-824, chlorpromazine (CPZ) or prostaglandin E2(PGE2). Both peptides also completely suppressed the PRL secretion induced by FK 33-824 or PGE2, and partially that induced by CPZ, but not that induced by domperidone. The intravenous administrations of CCK and bombesin had no or lesser potency in inhibiting the stimulated GH or PRL releases. These results indicate that the CCK and bombesin act much in the same manner to inhibit GH and PRL. These peptides may suppress the GH and PRL secretions via a hypothalamus-related action.

Anesthesia, General↗

PubMed1982

Effects of 2-nicotinamidoethyl nitrate on smooth muscle cells of the guinea-pig mesenteric and portal veins.

The effects of 2-nicotinamidoethyl nitrate (2-NN) on the smooth muscle cells of the guinea-pig mesenteric and portal veins were investigated by using an intracellular microelectrode technique and isometric tension recording method. In the mesenteric vein, 2-NN (greater than 1 x 10(-5) M) hyperpolarized the membrane in a manner dependent on the dose. The 2-NN-induced hyperpolarization was also dependent on the external K concentration, but was independent of the external Na and Cl concentrations. It was unaffected by removal of Ca from the external solution. Therefore, the hyperpolarization is thought to be due to an increase in the K conductance of the membrane. Excess [K]0 depolarized the membrane and produced contraction. Although 2-NN (1 x 10(-6) M) did not modify the depolarization induced by excess [K]0. It suppressed the contraction. Norepinephrine depolarized and acetylcholine hyperpolarized the membrane, whereas both agents produced small concentrations. 2-NN (1 x 10(-4) M) suppressed the membrane potential changes and contractions evoked by both agents. In the portal vein, 2-NN (1 x 10(-5) M) also hyperpolarized the membrane and abolished the spontaneous spike generation and contraction. 2-NN is more potent on the mesenteric and portal veins than on the mesenteric artery.

Acetylcholine↗

PubMed1981

Isoprenaline- and noradrenaline-induced hyperpolarization of guinea-pig liver cells.

1 Effects of pretreatment with isoprenaline (Isop) or noradrenaline (NA) and various ionic environments on the NA-induced or Isop-induced hyperpolarization of guinea-pig liver cells were investigated by means of a microelectrode technique.2 NA (5.9 x 10(-6) M) decreased the membrane resistance, and hyperpolarized the membrane with or without generation of an initial transient small depolarization. The NA-induced initial depolarization was not dependent on the membrane potential and was increased by Isop (4.0 x 10(-6) M) or glucagon (10(-7) M).3 In Ca-free solution, the NA-induced hyperpolarization became transient and a continuous depolarization followed in the presence of NA. Repetitive application of NA resulted in a complete disappearance of the NA-induced hyperpolarization and was replaced by a slowly developing depolarization with or without generation of the initial transient depolarization. In excess [Ca](o), the NA or Isop-induced hyperpolarization was increased.4 Both Isop and glucagon hyperpolarized the membrane and decreased the membrane resistance, to various degrees. Repetitive application of Isop or glucagon resulted in the disappearance of both Isop and glucagon-induced hyperpolarizations. Pretreatment with NA not only resulted in a recovery of both Isop and glucagon-induced hyperpolarizations, but also extensively enhanced the hyperpolarization.5 After pretreatment with Isop, the NA-induced hyperpolarization was decreased in amplitude and duration and was followed by a slowly developing depolarization. After repetitive application of Isop, NA produced only depolarization of the membrane, and in these conditions, Isop, glucagon or ATP also depolarized the membrane. These depolarizations were reversed to hyperpolarizations by pretreatment with excess [Ca](o).6 After treatment with Na-deficient solution, NA depolarized the membrane and decreased the membrane resistance. Excess [Ca](o) restored the NA-induced membrane response from one of depolarization to one of hyperpolarization.7 In the presence of tetraethylammonium 10mM, the NA-induced hyperpolarization became transient or ceased and depolarization occurred with a reduction in the membrane resistance.8 It is postulated that both NA and Isop increase the free [Ca](i) by releasing bound Ca from storage sites and consequently an increase in K conductance follows. NA but not Isop promotes Ca-influx which replenishes the storage site. In Ca-depleted conditions, NA does not elevate the free [Ca](i) to a threshold concentration required for hyperpolarization, probably because NA induces a small release of Ca from storage sites.

Action Potentials↗

PubMed1981

Effects of vasopressin on smooth muscle cells of guinea-pig mesenteric vessels.

1 The effects of vasopressin on the membrane and contractile properties of smooth muscle cells of guinea-pig mesenteric arteries, and mesenteric and portal veins were investigated in various ionic environments by means of a micro-electrode technique and an isometric tension recording method. The results were compared with those obtained with oxytocin and noradrenaline (NA).2 In the mesenteric jejunal artery, the mean membrane potential was -56.6 +/- 2.3 mV, s.d, and the membrane was electrically quiescent. Application of outward current pulses generated small graded responses, and the current voltage relationship was linear with application of an inward current pulse.3 Vasopressin and NA depolarized the membrane and increased the membrane resistance. Vasopressin was a 1000 times more potent than oxytocin in depolarizing the membrane. In high concentrations, vasopressin (1 x 10(-3) or 1 x 10(-2) iu/ml) or NA (5.9 x 10(-5) M) generated slow oscillatory membrane potential changes (slow waves) and spikes during the depolarization. The excitatory actions of vasopressin and NA were not suppressed by tetrodotoxin (3.1 x 10(-7) M) or ouabain (1.3 x 10(-6) M) and the actions of vasopressin were not suppressed by adrenoceptor blocking agents (3.9 x 10(-7) M phentolamine or 3.6 x 10(-7) M propranolol).4 The depolarization induced by vasopressin or NA is mainly due to a decrease in the K-permeability of the membrane. However, the contribution of other ionic species to the depolarization induced by vasopressin or NA differed, e.g. in low concentrations of [Na](o), the NA-induced depolarization was suppressed to a greater extent than that due to vasopressin. In low concentrations of [Ca](o), the vasopressin-induced depolarization was suppressed to a greater extent than with NA.5 In low concentrations of [Ca](o) and in the presence of vasopressin or NA, spike generation was inhibited but slow waves were not. In low concentrations of [Na](o), the vasopressin-induced slow waves and spikes were for the great part preserved, but with a high concentration of [Ca](o), vasopressing-induced slow waves were suppressed.6 Both vasopressin and NA produced contractions in the jejunal mesenteric artery. However, the maximum contraction in response to vasopressin was larger than that to NA, although both induced similar membrane depolarization. In a low concentration of [Na](o), vasopressin but not NA produced a contraction.7 In the cranial mesenteric artery, NA (5.9 x 10(-5) M) depolarized the membrane and produced a contraction, while vasopressin (1 x 10(-1) iu/ml) and oxytocin (1 x 10(-1) iu/ml) neither depolarized the member nor produced a contraction. In the mesenteric vein, NA (5.9 x 10(-5) M) slightly depolarized the membrane and produced a small contraction. On the other hand, in the portal vein, NA (5.9 x 10(-7) M) produced a marked depolarization and a contraction. Vasopressin (1 x 10(-1) iu/ml) and oxytocin (1 x 10(-1) iu/ml) produced neither excitatory nor inhibitory actions in these veins.8 It is concluded that vasopressin acts on only small muscular arteries, while NA acts on all mesenteric vessels, particularly the portal vein. Therefore, the hepatic portal vascular resistance may be increased by NA and reduced by vasopressin.

Animals↗

PubMed1981

Electrical properties of smooth muscle cell membrane and neuromuscular transmission in the guinea-pig basilar artery.

1 The membrane properties of smooth muscle cells and neuromuscular transmission in the guinea-pig basilar artery were investigated by use of microelectrodes.2 The membrane potential was -47.0 mV and the muscle tissue possessed cable-like properties as determined by the current-voltage relationships. The mean value of the spacè constant was 0.78 mm.3 An outward current produced a graded response and, in some cases, spike generation. This membrane response was enhanced in the presence of tetraethylammonium (TEA, 5 mM), and an increased concentration of TEA (10 mM) generated spontaneous spikes in most of the cells. Action potentials induced by TEA were abolished in the presence of MnCl(2) (5 mM) but not by isoprenaline (4 x 10(-6) M).4 Acetylcholine (ACh), over 10(-7) M, hyperpolarized the membrane and decreased the membrane resistance. This hyperpolarization increased in the presence of low [K](o) (below 5.9 mM), but decreased in [K](o) concentrations over 17.8 mM. Pretreatment with atropine (10(-6) M) suppressed the ACh-induced hyperpolarization. Therefore, this action of ACh is due to an increase in the K-conductance of the membrane produced by activation of the muscarinic receptors.5 Noradrenaline in concentrations up to 10(-4) M did not modify the membrane potential and resistance, while 10(-5) M, histamine, 5-hydroxytryptamine and adenosine triphosphate (ATP) depolarized the membrane. The depolarization induced by histamine or ATP was suppressed by reducing [Na](o). The histamine-induced depolarization was accompanied by an increase and the ATP-induced one by a decrease in the membrane resistance. The action of histamine was suppressed by treatment with H(1)- but not H(2)-receptor blocking agents (dephenhydramine and cimetidine, respectively).6 Perivascular nerve stimulation (0.2 ms pulse duration) evoked excitatory junction potentials (e.j.ps). An increase in the number and frequency of stimuli enhanced the e.j.p. amplitude. In the presence of 1 mM TEA, a spike was evoked on the e.j.ps. A very high concentration of phentolamine (3.6 x 10(-4) M) or the usual concentration of tetrodotoxin (10(-7) M) abolished the generation of e.j.ps. Spontaneously generated miniature e.j.ps were never recorded from the resting membrane.7 The results are discussed in relation to regional specificities of smooth muscle cells of cerebral arteries in the guinea-pig.

Acetylcholine↗