Increased beta I-adrenoceptor density after 6-hydroxydopamine pretreatment in rat colon and lung

Estimation of beta-adrenoceptor-binding sites with 125I-(-)-pindolol in rat colon show a proportion of 30% beta I-adrenoceptors and 70% beta 2-adrenoceptors. Studies on the isolated colon strip have revealed a neuronal beta-adrenoceptor involved in the inhibitory response of colon motility to beta-adrenoceptor stimulation. In order to further characterize the beta-adrenoceptors in the colon, acute and chronic treatments with 6-hydroxydopamine were made. Both acute pretreatment of rats with 6-hydroxydopamine for 8 and 24 h (one intravenous injection) and chronic treatment for 3 days (implanted osmotic mini-pumps), reduced the noradrenaline tissue content by 90%, and successively increased the beta-adrenoceptor-binding sites from 14.2 to 21.7 fmol mg-I P-I in colon and from 158 to 240 fmol mg-I P-I in lung membranes. Displacement of the radiolabelled ligand by the selective beta-adrenoceptor antagonists, pafenolol and ICI 118.551 showed that the density of beta I-adrenoceptor binding sites was more than doubled, whereas the density of beta 2-adrenoceptor-binding sites was only marginally increased by chronic treatment with 6-hydroxydopamine. Thus sympathetic denervation by 6-hydroxydopamine treatment produced a selective increase in beta I-adrenoceptors in the rat colon. These results may indicate that stimulation of beta I-adrenoceptors in both colon and lung have a neuronal linkage.     

Density and functioning of human lymphocytic β-adrenergic receptors during prolonged physical exercise

In order to study the regulation of β-adrenergic receptor number and function in response to prolonged physical effort, lymphocytic β-adrenoceptor density (determined by (-)[¹²⁵I]iodocyanopindolol binding), lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and concentrations of plasma catecholamines were measured before and during 3 h running exercise in eight healthy volunteers. A significant (P < 0.01) increase of the lymphocytic β-adrenoceptor density from 45±4 to 81 ± 9 fmol mg^-1 protein (mean ± SEM) took place during the first hour of exercise. As the exercise was continued for up to 2.1–3 h, the receptor densities did not change significantly any more and remained elevated (72 ± 9 fmol mg^-1 protein) in comparison to the resting levels (P < 0.02). The isoproterenol-stimulated cAMP production of the lymphocytes increased during the first hour of running from 190 ± 36 to 269 ± 56 pmol mg^-1 protein (P < 0.01) and returned to the resting level at the end of the exercise (182 ± 38 pmol mg^-1 protein). The mean levels of plasma catecholamines increased ? sixfold during the first hour of exercise and remained elevated until the end of the running. This study demonstrates that the β-adrenergic receptor system is activated in lymphocytes during prolonged aerobic physical exercise. This activated state becomes, however, attenuated within 2–3 h of exercise as indicated by a diminishing ability of β-adrenoceptors to mediate catecholamine-induced cAMP production.     

Autoradiographic location of β-adrenoceptor subtypes in cat colon smooth muscle

In order to localize β-adrenoceptors ¹²⁵I-(—)pindolol (IPIN) was used in binding to sections from cat colon. The binding characteristics for IPIN to β-adrenoceptors on colon sections were estimated by demonstrating reversible binding in the presence of isoprenaline and by steroselective binding to the isomers of propranolol. The binding of IPIN to both β₁-and β₂-adrenoceptors was shown by biphasic displacement curves in the presence of the selective β-adrenoceptor compounds betaxolol, ICI 118.551 and procaterol. The colon sections were found to contain proportions of β₁-adrenoceptors (30–50%) and β₂-adrenoceptors (50–70%). In the autoradiographic studies, 100% of the developed grains after exposure of IPIN to the photographic emulsion were displaced by 50 μm of isoprenaline. By microscopic counting at autoradiographic grains, 30–40% of the grains were found in the circular smooth muscle, while 60–70% of the grains were found in the longitudinal smooth muscle. A concentration of 2 nm ICI 118.551 completely displaced all grains in the circular smooth muscle and partly displaced those found in the longitudinal smooth muscle. A high concentration of ICI 118.551 (1 μm ) displaced all grains above background from the smooth muscle. It is concluded that the circular smooth muscle only contains β₂-adrenoceptors, while longitudinal smooth muscle may contain a proportion of β₁-adrenoceptors. Whether such a location of β-adrenoceptors can be related to the β₁-adrenoceptor-mediated inhibition of colon motility can not be clarified from these studies. However, it seems that β₁-adrenoceptors are located to the longitudinal smooth muscle instead of to the myenteric plexus of the colon.     

Some alterations of the leucoeyte β2-adrenoceptor/cAMP-system in patients with seasonal allergic rhinoconjunctivitis are related to disease activity

Background Disturbances of β₂-adrenoceptors are discussed as a pathogenic factor in atopic diseases. Methods In this study tbe expression and function of β₂-adrenoceptors on peripheral blood leucocytes (PBL) of seven atopic patients with seasonal rhinoconjunctivitis and their seven healthy controls was evaluated in relation to disease activity. Earlier reported data during pollen. season were now compared with data obtained from the same subjects after their allergic symptoms had subsided. Results The variables that had indicated a β₂-adrenoceptor subsensitivity in tbe patients during pollen season returned to control values, i.e. the reduced β₂-adrenoceptor affinity, the reduced β₂-adrenoceptor sensitivity, the reduced increase of intracellular cyclic adenosine monophosphate (cAMP) content upon stimulation with isoproterenol, and the reduced cAMP plasma concentration (values no longer significantly different from those of controls). However, the variable that had suggested an increase in activity of the cAMP degrading enzyme phosphodiesterase (PDE), i.e. the reduced basal intracellular cAMP content of the patients, remained reduced after the pollen season (4.9 ± 1.1 pmol/lO⁶’cells in patients vs 8.2 ^± 0.9pmol/10⁶ cells in controls: P < 0.05). There were no significant differences in β₂-adrenoceptor density between patients and controls at both investigations. Conclusions Atopic seasonal rhinoconjunctivitis is associated with various alterations in the PBL β_2-adrenoceptor/cAMP system that depend on disease activity. The reversible β₂-adrenoceptor subsensitivity is likely to be a consequence of the disease, whereas the irreversibly decreased basal intracellular cAMP content, suggested an elevated PDE activity, might be a basic trait of atopy.     

The importance of an intact sympathetic innervation for the differentiation of the β-adrenoceptor subtypes in the rat parotid gland

Acinar cells of the rat parotid gland are in intimate contact with adrenergic nerves, arousing from the ganglion cervicale superior (Bloom et al. 1977). The sympathetic nerves or circulating catecholamines exert their effects by activating α-adrenoceptors (electrolyte and water secretion) or β-adrenoceptors (enzyme secretion) (Batzri et al. 1971, Carlsöö et al. 1981). It is now well established that the β-adrenoceptors can be divided in two subclasses, β₁ and β₂, present in different proportions depending on the tissue examined (Lands et al. 1967, Carlsson et al. 1972, Barnett et al. 1978, Minneman et al. 1979a). The concentrations of the two subtypes are regulated independently (Minneman et al. 1979b) and their molecular structure seems to be different (Venter et al. 1981). The β₁, -subtype is dominating in normal rat parotid glands (Carlsöö et al. 1981, Ludford & Talamo 1980). Supersensitivity occuring in salivary glands after interruption of the sympathetic nerve supply in adult animals is usually associated with an increased number of the β-adrenoceptors (Ludford & Talamo 1980, Stefano & Perec 1981). In the present work we have studied the effect of neonatal sympathetic denervation of the rat parotid gland on the binding of the β-adrenoceptor radioligand ³H-dihydroalprenolol (³H-DHA) and on the β-adrenoceptor-induced amylase secretion. The results suggest that the normal dominance of the β₁-adrenoceptors is lost after neonatal sympathetic denervation. Hence, an intact sympathetic nervous system may be of major importance during the development of the β-adrenoceptor population.     

Prejunctional β2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ

Prejunctional β-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood-perfused canine gracilis muscle in situ. An attempt was made to subclassify these β-adrenoceptors by comparing the effects of β₁-selective (metoprolol) and non-selective (propranolol) β-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation-evoked NA overflow, as compared with control experiments (?10 and ?8 %, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P < 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post-junctional β₁-as well as β₂-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional β₂-adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional β₂-adrenoceptors in vivo.     

Comparison of β-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle

Blood flow changes in response to various drugs in simultaneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular β-adrenoceptors. Compared to isoprenaline the β₂-selective agonist salbutamol was 4–6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two β₁-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after β-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before β-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the β-adrenoceptors mediating vasodilatation in skeletal muscle are mainly of the β₂-type, whereas β₁-adrenoceptors seem to predominate in subcutaneous adipose tissue. Since adrenaline is a much more potent β₂- than β₁-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor.     

Microsphere analysis of β2-adrenergic control of resistance in different vascular areas after hemorrhage

In cats exposed to bleeding (exsanguination of 15 ml×kg bwt^-1) the microsphere technique was used to determine regional vascular resistances in a large number of tissues before and after i.v. administration of the ‘selective’β₂-adrenoceptor antagonist ICI 118,551. β₂-blockade significantly raised vascular resistance in the stomach (+26%), small (+25%) and large (+38%) intestine, pancreas (+29%), kidney (+39%), omental (+33%) and subcutaneous (+26%) fat, ‘white’ skeletal muscle (+19%), and skin (+24%). These findings indicate that, with intact β-adrenoceptors, β₂-adrenergic dilator interaction counteracted the hemorrhage evoked vasoconstrictor influences. β₂-blockade also evoked quite a strong increase of total peripheral resistance (19%) and led to some redistribution of cardiac output. It is concluded that β₂-adrenergic inhibition of vascular tone significantly seems to improve tissue perfusion during bleeding in several vascular areas. Such effects may be of special significance during severe hemorrhage. In the intestine, pancreas, and adipose tissue, for example, protection against excessive vasoconstriction may serve to minimize the severe metabolic disturbances with secondary release of toxic factors into the circulation reported during hemorrhagic shock.     

Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of β-adrenoceptors

The present experiments were undertaken to study the balance between vascular α- and β-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the β-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The β₁-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during α-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaiine and nerve stimulation. The β₂-selective antagonist H35/25 blocked the effects of the β₂-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic β-adrenoceptor responses. The present results provide further support for the hypothesis that vascular β-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic β-adrenoceptors activated by noradrenaline in adipose tissue are best classified as β₁-adrenoceptors.     

The influence of vascular β-adrenoceptors on the position and mobility of the rabbit incisor tooth

The influence of vascular β-adrenoceptors on the tooth-supporting functions of the periodontal ligament were studied in 30 anesthetized rabbits. Propranolol and the β₂-adrenoceptor antagonists ICI 118,551 and H 35/25 induced a marked extrusion of the incisor, probably due to reduced vasodilator tone in periodontal postcapillary blood vessels. Isoprenaline reversed the movement. β₁- and β₂-receptor antagonists decreased the intrusive responses to sympathetic nerve stimulation in teeth close to control position, but had no effect on responses in fully extruded teeth. Intrusive mobility, as tested by intermittent loading with 5–10 g, remained unaffected by β-adrenoceptor blockade. The results suggest that vascular β₂-adrenoceptors are important in the regulation of tooth position by their control of periodontal postcapillary resistance. Prejunctional β-receptors enhancing the vasoconstrictor - and intrusive - responses to sympathetic nerve stimulation are probably a mixture of β₁- and β₂-receptors. It would seem that the periodontal vasculature is important for the position of the rabbit tooth but, due to rapid adaptive mechanisms of the tooth-supporting tissues, the vasculature contributes little to the resistance against loadinduced intrusive movements of the tooth.     

Influence of angiotensin II, α- and β-adrenoceptors on peripheral noradrenergic neurotransmission in canine gracilis muscle in vivo

Interactions between angiotensin II and adrenoceptor-mediated effects on peripheral sympathetic neurotransmission were investigated in constant flow blood-perfused canine gracilis muscle in situ, without and with pretreatment by non-competitive α- adrenoceptor blockade. Angiotensin converting enzyme (ACE)-inhibition by benazeprilat increased nerve stimulation (2 Hz, 4 min)-evoked noradrenaline (NA) overflow (+21 ± 5 yo) with α- adrenoceptors intact, but reduced NA overflow (– 18 ± 6%) when α-adrenoceptors were blocked. Vasoconstrictor responses were slightly reduced by benazeprilat. Subsequent infusion of angiotensin II (Ang 11, 20 and 500 ng kg_-1 min_-1 i.v., raising arterial concentrations from 0.6 ± 0.2 PM to 1390 ± 240 and 25 110 ± 3980 PM, respectively) failed to increase NA overflow or to enhance stimulation-evoked vasoconstriction. Adrenaline (0.4 nmol kg_-1 min_-1 i.v.) did not change evoked NA overflow before or after benazeprilat, either with or without α-adrenoceptor blockade, despite high concentrations (± 10 nM) in arterial plasma. Following benazeprilat, propranolol reduced NA overflow (–24 ± 3 yo) only if the α-adrenoceptors were blocked. In conclusion, benazeprilat reduced evoked NA overflow in the presence of α- adrenoceptor blockade to a similar degree as previously shown in the presence of neuronal uptake inhibition in this model. However, contrasting to our previous findings, benazeprilat enhanced NA overflow and reduced the post-junctional response to nerve stimulation in the absence of α-adrenoceptor blockade. This could be related to bradykinin accumulation during ACE-inhibition, in addition to the reduction of Ang II generation. Our data are not compatible with facilitation of NA release by circulating Ang II even at pharmacological dose levels. Although activation of prejunctional β-adrenoceptors may facilitate evoked NA overflow in this model, circulating adrenaline is ineffective under physiological conditions even after α-adrenoceptor blockade. Also, β-adrenoceptor-mediated prejunctional effects do not seem to involve Ang II in canine skeletal muscle in vivo.     

Comparison of beta-adrenoceptors in bovine intracerebral microvessels and cerebral grey matter by [3H]dihydroalprenolol binding

Intracerebral microvessels were isolated from bovine brain by a sieving technique and membranes prepared from them were examined for β-adrenoceptors using the radioligand (?)-[³H]dihydroalprenolol. Binding of (?)-[³H]dihydroalpenolol was rapid and reversible and also saturable with increasing concentration of the radioligand. (?)-[³H]Dihydroalprenolol bound to a single high affinity site which displayed stereoselectivity for the (?) isomer of propranolol relative to its (+) isomer. Thus the characteristics of (?)-[³H]dihydroalprenolol binding to microvessel membranes were consistent with binding to β-adrenoceptors. The concentration of β-adrenoceptor sites in cortical microvessel membranes was approximately half that in cortical grey matter membranes, whilst the affinity of (?)-[³H]dihydroalpenolol binding to cortical microvessels was six times greater than for the corresponding binding in cortical grey matter. The density of binding sites in microvessels isolated by the same method from bovine striatal and hippocampal grey matter was similar to that in microvessels obtained from cortical grey matter.These results demonstrate that bovine intracerebral microvessels contain significant numbers of β-adrenoceptors and strengthen the hypothesis that neurotransmitters and vasoactive substances such as noradrenaline and adrenaline may regulate the calibre of intracerebral blood vessels.     

β-adrenoceptor agonists do not cause tremor in the conscious rat

The ability of some β-adrenoceptor agonists to induce tremor via skeletal muscle β₂-adrenoceptors in conscious unrestrained rats has been investigated. Tremor was assessed by visual observation and by an objective method based on accelerometry. Infusion of isoprenaline or terbutaline did not cause tremor, neither did β-stimulation potentiate an established mild tremor produced by central muscarinic receptor stimulation. Since β-agonists readily produce tremor in man via skeletal muscle β₂-adrenoceptor stimulation, our findings indicate that these receptors have a different function in the rat.     

Modulation of oxotremorine-induced tremor by central β-adrenoceptors

The muscarinic agonist oxotremorine was used to induce tremor in rats pretreated with methylatropine. An objective assessment of tremor intensity was accomplished by means of an accelerometer-based recording system. The non-selective, lipophilic β-adrenoceptor antagonist propranolol dose-dependently suppressed tremor intensity, whereas the r -isomer of propranolol was without effect, verifying β-adrenoceptor involvement. Since the hydrophilic, non-selective β-antagonist nadolol was ineffective, the effect appears to be located inside the blood-brain barrier. The β₂-selective antagonist ICI 118, 551 dose-dependently reduced tremor intensity, whereas selective blockade of β₁-adrenoceptors with metoprolol had no effect, indicating the participation of a β₂-adrenoceptor. On the other hand, the lipophilic β₂-agonist clenbuterol dose-dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of β-antagonists on tremor was not secondary to an effect on the oxotremorine-induced rise in catecholamine levels. Thus, the results suggest that β₂-adrenocpetors located inside the blood-brain barrier are able to modulate oxotremorine-induced tremor in rats.     

Functional β1 - and β2-adrenoceptors in the human myocardium

Functional β-adrenoceptor populations in the human heart were studied in vitro in electrically-paced strips of the right auricular and ventricular myocardium. The relative potency of selected agonists in producing inotropic responses (T_max, T′_max) in the presence of blockers for neuronal and extraneuronal uptakes was found to be as follows: isoprenaline > noradrenaline = adrenaline = salbutamol > dobutamine. Prenalterol had a negative inotropic effect in these preparations. The selective β₁ -(practoloI) and β₂-(H 35/25) blockers reduced inotropic responses to adrenaline (T_max, T′_max) and noradrenaline (T′_max) in the auricular strips. These results indicate the participation of β₂-adrenoceptors in inotropic responses in the human auricular and ventricular myocardium. For comparison, inotropic responses of electrically-paced rat myocardium to β-adrenergic agonists in the presence of blockers for neuronal and extraneuronal uptakes were likewise studied. The relative potencies for T_max were: noradrenaline = adrenaline > prenalterol > dobutamine = salbutamol. Given the high relative potency of salbutamol in the human myocardial strips (analogous to that previous shown in the β₂-dominated atria of the frog and trout) and the low relative potency of salbutamol in the rat tissue, these findings indicate a greater population of functionally active β₂-adrenoceptors in the human than in the rat myocardium.     

Blockade of central β-adrenoceptors attenuates tremor induced by 5-hydroxytryptamine (5-HT)-receptor activation in rats

The effect of β-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by l -5-hydroxytryptophan (L-5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist s-methoxy-N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the β-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, β₁-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the β₂-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the β-adrenoceptor subtype involved is of the β₂-type. These results suggest that blockade of centrally located β₂-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation.     

The effect of repeated mild stress on cerebral cortical adrenoceptors and noradrenaline synthesis in the rat

The effects of repeated mild stress on cortical α₂- and β-adrenoceptor binding sites and on the rate of noradrenaline synthesis in cortical synaptosomes were measured. The stressful stimuli were either daily handling (1 min) or daily handling which included an i.p. saline injection. In both cases, rats killed 24 h after the last of 14 daily treatments showed an increase in noradrenaline synthesis rate and a decrease of α₂- and β-adrenoceptor density. There were no changes in adrenoceptor density or the noradrenaline synthesis rate after either a single or 5 daily handlings plus saline injections. At no time was a change found in the K_d of either α₂- or β-adrenoceptor binding sites. The results are discussed in relation to the effects on adrenoceptors of chronic antidepressant treatments.     

Identification ofβ 2-adrenoceptors on guinea pig alveolar macrophages using (−)-3-[125I]iodocyanopindolol

The -adrenoceptor antagonist (–)-3-[¹²⁵I]iodocyanopindolol ([¹²⁵I]ICYP) binds with high affinity and in a saturable way to membranes of guinea pig alveolar macrophages. The equilibrium dissociation constant for [¹²⁵I]ICYP is 24.3 ± 1.2 pM, and the number of binding sites is 166.3 ± 13.7 fmol/mg protein (N=4, ±SEM). Displacement studies with selective antagonists showed that [¹²⁵I]ICYP labels ₂-adrenoceptors on guinea pig alveolar macrophages.     

VIP inhibition of vascular smooth muscle: complementary to β2-adrenoceptor mediated relaxation in the isolated rat portal vein

Exogenous VIP caused a concentration dependent inhibition of the spontaneous mechanical activity in the isolated rat mesenteric-portal vein preparation via a mechanism which was completely independent of the propranolol-blocked β-adrenoceptor, of high K⁺ in the medium and of exogenous bovine pancreatic polypeptide, neurotensin and opioids. The potency of VIP ((pD₂=7.52±0.18, n=6) was about 30 times higher than that of isoprenaline in the atropine and phentolamine-blocked preparation. The isoprenaline inhibition was mediated via a β₂-type of adrenoceptor with low apparent affinity for noradrenaline (intrinsic activity (a) = 0.27±0.01, n=8). Opposite effects of exogenous VIP and noradrenaline were on the other hand observed in the atropinized and β-blocked preparation. These results suggest that in the rat portal vein neuronal VIP and circulating adrenaline may be complementary in their antagonism of the α-adrenoceptor mediated increase in contractility.     

Effects of selective α1 and α2 adrenoceptor active drugs on 86Rb+ efflux from pieces of rat parotid gland

Minute pieces of rat parotid gland were used in studies of adrenergic regulation of K+ efflux using ⁸⁶Rb+ as a probe for K+. Noradrenaline induced a concentration-dependent Rb+ efflux, whereas the β₁-selective agonist prenalterol was without effect. On the other hand, the β₂-selective drug, terbutaline, at high concentrations displayed a small enhancement of Rb+ -secretion. The selective α₁-adrenoceptor drug, phenylephrine, was as potent as noradrenaline, whereas the α₂-agonist clonidine had only a small effect. The noradrenaline-induced Rb+-efflux was effectively inhibited in the presence of prazosin, an α₁-blocker, whereas the α₂-antagonist, yohimbine, was roughly 50 times less potent. The results suggest that catecholamine-induced K+-secretion from the rat parotid gland is mediated via activation of post-synaptic α-adrenoceptors of the α₁-subtype.